KR20090061160A - Biomarker for confirming exposure of indeno (1,2,3-c, d) pyrene and method for identifying using same - Google Patents

Abstract

The present invention is a biomarker for checking the exposure to indeno (1,2,3-c, d) pyrene (Indeno [1,2,3-c, d] pyrene) which is one of the polycyclic aromatic hydrocarbons and The present invention relates to a biomarker that specifically increases or decreases gene expression by indeno (1,2,3-c, d) pyrene and an indeno (1,2,3-) using the same. c, d) relates to a method for confirming exposure to pyrene, and the biomarker of the present invention uses an indeno (1,2, It can be useful for monitoring and determining the contamination of 3-c, d) pyrene and as a tool to identify the mechanism of toxic effects caused by indeno (1,2,3-c, d) pyrene. Can be.

Description

Biomarker for identification of indene (1,2,3-c, d) pyrene exposure and identification method using same {Biomarker for identification of exposure to Indeno [1,2,3-c, d] pyrene and the method of identification using Julia}

The present invention relates to a biomarker for confirming exposure to indeno [1,2,3-c, d] pyrene and a method of identifying the same, More specifically, biomarkers in which gene expression is increased or decreased by indeno (1,2,3-c, d) pyrene and indeno (1,2,3-c, d) pyrene using the same It relates to how to check the exposure.

Among polycyclic aromatic hydrocarbons, indeno (1,2,3-c, d) pyrene is mainly emitted from the atmosphere in the environment. Indeno (1,2,3-c, d) pyrene is not a commercially produced material but is mainly produced for research purposes and is known to be used in dye production abroad.

Indeno (1,2,3-c, d) pyrene has a low affinity for low aquatic life and high affinity for organisms in low quality, soil and biomass. Accumulate. Photolysis and microbial degradation and microbial degradation occurs under aerobic conditions. The half-life by reaction with OH radicals suspended in the atmosphere is about 1 day. It is also strongly adsorbed by sunlight, causing a direct photolysis reaction in the environment.

Inferred from the data of structurally similar PAH, mainly benzo [a] pyrene, indeno (1,2,3-c, d) pyrene is absorbed into the gastrointestinal tract, lungs and skin. You can think about it. The most common metabolite found in the skin of mice is 8-hydroxyindeno (1,2,3-c, d) pyrene, in addition to 9-hydroxyindeno (1,2,3-c, d ) Pyrene, trans-1,2-dihydro-1,2-dihydroxyindeno (1,2,3-c, d) pyrene, and the like. Unlike ordinary PAH, indeno (1,2,3-c, d) pyrene does not have a bay region, so it is not simply activated by the bay region epoxide, but 1,2-diol and its epoxide precursor 1, It is known to have similar carcinogenicity in 2-epoxides.

Although some studies on the degree of carcinogenicity and gene expression of polycyclic aromatic hydrocarbons have been reported, they are almost limited to the study of benzo [a] pyrene, which is known as a representative polycyclic aromatic hydrocarbons. In spite of the possibility of carcinogenicity of indeno (1,2,3-c, d) pyrene in humans, there is not enough risk assessment data in humans, and the detection method for exposure is also GC-MS (Gas Chromatography). It is limited to classical methods such as Mass Spectrometer (HPM) or High Performance Liquid Chromatography (HPLC). Quantification is possible using GC-MS or HPLC methods, but appropriate conditions for analysis are required and expensive equipment is required. Therefore, faster and easier screening methods, such as real-time reverse transcript polymerase chain reaction (PCR) or DNA microarray chips using primers, can be used in humans through rapid risk assessment. It is an important task to identify and utilize molecular indicators that can explore the toxic effects of chlorine, and to take appropriate measures and control against the exposure of indeno (1,2,3-c, d) pyrene.

Several genome sequencing projects, including six mammals and 292 microbes, have been completed and reported to the National Center for Biotechnology Information (NCBI). Genome-wide expression studies are being conducted to study the function of genes based on the vast amount of data obtained. DNA microarray analysis is performed to analyze the expression of thousands of genes in one experiment (Schena, M., et al. , Proc. Natl. Acad. Sci. USA 93: 10614-10619, 1996). .

Microarrays integrate a set of oligonucleotides of complementary DNA (cDNA) or 20-25 base pairs in length on glass. cDNA microarrays are produced by labs in schools or by companies such as Agilent and Genomic Solutions, either mechanically immobilizing the cDNA collection on a chip or by using ink jetting (Sellheyer K. et. al., J. Am). . Acad Dermatol 51:.. 681-692 , 2004). Oligonucleotide microarrays are made by Affymetrix by direct synthesis on a chip using photolithography, and Agillent et al. Are produced by immobilizing synthesized oligonucleotides (Sellheyer, K.). et. al., J. Am. Acad. Dermatol . 51: 681-692, 2004).

For gene expression analysis, RNA is obtained from samples such as tissues and hybridized with oligonucleotides in a DNA microarray. The resulting RNA is labeled with fluorescence or isotope and converted to cDNA. Oligo microarrays are mainly labeled with two different fluorescences (eg, Cye3 and Cye5) to perform hybridization reactions on the same chip at the same time. . Gene expression is determined according to the ratio of the two fluorescence intensities (Somasundaram, K. et al. , Genomics Proteomics I: 1-10, 2002).

In combination with recent research on toxic genomics (Toxicogenomics), an advanced technique using DNA macroarray technology, high-throughput expression in specific tissues or cell lines by all chemicals, including pharmaceuticals and new drug candidates, as well as representative environmental pollutants Analysis and quantitative analysis of expression patterns of genes are now possible. Accordingly, by analyzing the frequency of expression of specific genes in specific cells, it is possible to discover genes related to adverse effects of drugs and harmful effects of environmental pollutants, and through this, molecules according to the harmful effects of environmental pollutants, drugs, and side effects. It will be possible to understand the mechanisms and further to search for substances that cause toxicity and side effects.

Therefore, the present inventors observed and analyzed a gene expression profile of indeno (1,2,3-c, d) pyrene in HepG2 cell line, which is a human liver cancer cell, using an oligomicroarray of 44,000 human genes. Biomarkers capable of detecting indeno (1,2,3-c, d) pyrene by discovering genes overexpressed or underexpressed by indeno (1,2,3-c, d) pyrene and the same The present invention was completed by establishing a method of confirming whether or not exposure was used.

An object of the present invention is a biomarker that is overexpressed or underexpressed by exposure to indeno (1,2,3-c, d) pyrene and indeno (1,2,3-c, d) using the biomarker. It provides a way to check for exposure to pyrene.

In order to achieve the above object, the present invention is characterized by causing the expression change by exposure to Indeno (1,2,3-c, d) pyrene (Indeno [1,2,3-c, d] pyrene) It provides a biomarker for confirming the exposure to indeno (1,2,3-c, d) pyrene.

In addition, the present invention is a DNA microorganism for confirming exposure to indeno (1,2,3-c, d) pyrene in which oligonucleotides or their complementary strand molecules containing all or part of the biomarker gene sequence are integrated Provides an array chip.

In addition, the present invention provides a method for confirming exposure to indeno (1,2,3-c, d) pyrene using the biomarker.

In addition, the present invention provides a search kit for confirming exposure to indeno (1,2,3-c, d) pyrene.

The biomarker for confirming the exposure to indeno (1,2,3-c, d) pyrene of the present invention and the method of confirming the same using the same are represented by indeno using a reaction gene selected through a DNA microarray chip as a biomarker. Useful for monitoring and risk assessment of (1,2,3-c, d) pyrene and as a tool to identify toxic effects caused by indeno (1,2,3-c, d) pyrene It is available.

Hereinafter, the present invention will be described in detail.

The present invention is to determine whether the exposure to indeno (1,2,3-c, d) pyrene, characterized in that the expression changes by the exposure of indeno (1,2,3-c, d) pyrene It provides a biomarker for.

The biomarker is a gene whose expression is increased or decreased 1.5 times or more, and includes cell death, zinc-finger, enzyme regulator activity, cell proliferation, and transcriptional regulation. (regulation of Transcription), oxidoreductase activity, ligase activity, immune response, signal transducer activity, cytoskeleton, macromolecular degradation (macromolecule catabolism) ), DNA binding, cell cycle, DNA repair, Zinc-finger, ATP binding, kinase activity, RNA processing (RNA) It consists of related genes such as processing, transport, signal transduction, and cytokine-cytokine receptor interactions.

The present invention provides a biomarker which is selected from the group consisting of:

Genebank (Genebank) NM_000606 (C8G, complement component 8, gamma polypeptide), Genebank (Genebank) NM_001429 (EP300, E1A binding protein p300), Genebank (Menebank) NM_003804 (RIPK1, receptor (TNFRSF) -interacting serine-threonine kinase 1), Genebank NM_003806 (HRK, harakiri, BCL2 interacting protein (contains only BH3 domain)), Genebank NM_003901 (SGPL1, sphingosine-1-phosphate lyase 1), Gene Registration Number (Genebank) NM_004049 (BCL2A1, BCL2-related protein A1), Gene Registration Number (Genebank) NM_006437 (PARP4, poly (ADP-ribose) polymerase family, member 4), Gene Registration Number (Genebank) NM_020371 (AVEN, apoptosis , caspase activation inhibitor), genebank NM_022094 (CIDEC, cell death-inducing DFFA-like effector c), genebank NM_022151 (MOAP1, modulator of apoptosis 1), genebank NM_133369 (UNC5A, unc-5 homolog A (C. Elegans)), genes, etc. (Genebank) NM_138578 (BCL2L1, BCL2-like 1), Gene Registration Number (Genebank) AB040944 (ZSWIM5, zinc finger, SWIM-type containing 5), Gene Registration Number (Genebank) AF144233 (ZMYND8, zinc finger, MYND- type containing 8), gene registration number (Genebank) NM_000176 (NR3C1, nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor)), gene registration number (Genebank) NM_002180 (IGHMBP2, immunoglobulin mu binding protein 2), gene registration Number (Genebank) NM_006254 (PRKCD, protein kinase c, delta), gene registration number (Genebank) NM_016213 (TRIP4, thyroid hormone receptor interactor 4), gene registration number (Genebank) NM_019062 (RNF186, ring finger protein 186), gene registration Number (Genebank) NM_022482 (GZF1, GDNF-inducible zinc finger protein 1), Gene Registration Number (Genebank) NM_033092 (TRIM5, tripartite motif-containing 5), Gene Registration Number (Genebank) NM_138287 (DTX3L, deltex 3-like (Drosophila) ), Gene Registration Number (Genebank) NM_145288 (ZNF342, zinc finger pro tein 342), Genebank NM_173548 (ZNF584, zinc finger protein 584), Genebank XM_930521 (ZNF506, zinc finger protein 506), Genebank BX648244 (SPATA13, spermatogenesis associated 13) , Gene Registration Number (Genebank) CR599277 (SERPINB2, serpin peptidase inhibitor, clade B (ovalbumin), member 2), Gene Registration Number (Genebank) NM_000308 (CTSA, cathepsin A), Gene Registration Number (Genebank) NM_001002857 (ANXA2, annexin A2), gene registration number (Genebank) NM_001320 (CSNK2B, casein kinase 2, beta polypeptide), gene registration number (Genebank) NM_001750 (CAST, calpastatin), gene registration number (Genebank) NM_004152 (OAZ1, ornithine decarboxylase antizyme 1), Gene Registration Number (Genebank) NM_006869 (CENTA1, centaurin, alpha 1), Gene Registration Number (Genebank) NM_014889 (PITRM1, pitrilysin metallopeptidase 1), Gene Registration Number (Genebank) NM_014916 (LMTK2, lemur tyrosine kinase 2) (Genebank) NM_015941 (AT P6V1H, ATPase, H + transporting, lysosomal 50 / 57kDa, V1 subunit H), Genebank NM_018482 (DDEF1, development and differentiation enhancing factor 1), Genebank NM_018993 (RIN2, Ras and Rab interactor 2 ), Gene Registration Number (Genebank) NM_032258 (TBC1D3, TBC1 domain family, member 3), Gene Registration Number (Genebank) NM_058197 (CDKN2A, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)), Gene Registration Number ( Genebank) NM_198681 (PLEKHG5, pleckstrin homology domain containing, family G (with RhoGef domain) member 5), Genebank BC002828 (AGGF1, angiogenic factor with G patch and FHA domains 1), Genebank NM_000875 (IGF1R, insulin-like growth factor 1 receptor), genebank NM_001562 (IL18, interleukin 18 (interferon-gamma-inducing factor)), genebank NM_002831 (PTPN6, protein tyrosine phosphatase, non- receptor type 6), gene registration number (Geneb) ank) NM_003999 (OSMR, oncostatin M receptor), genebank (Genebank) NM_004624 (VIPR1, vasoactive intestinal peptide receptor 1), genebank (Genebank) NM_005557 (KRT16, keratin 16 (focal non-epidermolytic palmoplantar keratoderma), Genebank (Genebank) NM_005755 (EBI3, Epstein-Barr virus induced gene 3), Genebank (Genebank) NM_007063 (TBC1D8, TBC1 domain family, member 8 (with GRAM domain)), Genebank (Genebank) NM_016558 ( SCAND1, SCAN domain containing 1), Genebank NM_032965 (CCL15, chemokine (CC motif) ligand 15), Genebank AF343007 (FOXC1, forkhead box C1), Genebank AK074757 (Genebank) ZNF253, zinc finger protein 253), genebank BC063666 (CREB3L2, cAMP responsive element binding protein 3-like 2), genebank NM_001010926 (HES5, hairy and enhancer of split 5 (Drosophila)), Genebank NM_002167 (ID3, inhibitor of DNA binding 3, dominant negative helix-loop-helix protein), Genebank NM_002501 (NFIX, nuclear factor I / X (CCAAT-binding transcription factor)), Genebank NM_003107 (SOX4, SRY ( sex determining region Y) -box 4), Genebank NM_003475 (RASSF7, Ras association (RalGDS / AF-6) domain family 7), Genebank NM_005315 (GSCL, goosecoid-like), Gene Genebank NM_005848 (DENND4A, DENN / MADD domain containing 4A), Gene Registration Number (Genebank) NM_005902 (SMAD3, SMAD family member 3), Genebank NM_006663 (PPP1R13L, protein phosphatase 1, regulatory (inhibitor) ) subunit 13 like), genebank NM_007005 (TLE4, transducin-like enhancer of split 4 (E (sp1) homolog, Drosophila)), genebank NG_012240 (SIRT4, sirtuin (silent mating type information) regulation 2 homolog) 4 (S. cerevisiae)), Genebank NM_014368 (LHX6, LIM homeobox 6), Genebank NM_015481 (ZNF385, zinc finger protein 385), Genebank NM_016170 (TLX2, T-cell leukemia homeobox 2), gene registration number (Genebank) NM_021961 (TEAD1, TEA domain family member 1 (SV40 transcriptional enhancer factor)), gene registration number (Genebank) NM_130439 (MXI1, MAX interactor 1), gene registration number (Genebank) NM_152287 (ZNF276 , zinc finger protein 276), genebank NM_207305 (FOXD4, forkhead box D4), genebank BC035714 (CYP19A1, cytochrome P450, family 19, subfamily A, polypeptide 1), gene registry ( Genebank) NM_000603 (NOS3, nitric oxide synthase 3 (endothelial cell)), gene accession number (Genebank) NM_000761 (CYP1A2, cytochrome P450, family 1, subfamily A, polypeptide 2), gene accession number (Genebank) NM_001013660 (FRRS1, ferric -chelate reductase 1), gene accession number (Genebank) NM_004542 ( NDUFA3, NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 3,9kDa), gene registration number (Genebank) NM_005390 (PDHA2, pyruvate dehydrogenase (lipoamide) alpha 2), gene registration number (Genebank) NM_005625 (SDCBP, syndecan binding protein (syntenin) )), Gene Registration Number (Genebank) NM_006157 (NELL1, NEL-like 1 (chicken)), Gene Registration Number (Genebank) NM_017460 (CYP3A4, cytochrome P450, family 3, subfamily A, polypeptide 4), Gene Registration Number (Genebank) ) NM_019885 (CYP26B1, cytochrome P450, family 26, subfamily B, polypeptide 1), Genebank NM_022051 (EGLN1, egl nine homolog 1 (C. elegans)), gene registration number (Genebank) NM_032783 (CBR4, carbonyl reductase 4), gene registration number (Genebank) NM_145690 (YWHAZ, tyrosine 3-monooxygenase / tryptophan 5-monooxygenase activation protein, zeta polypeptide), gene registration number (Genebank) ) NM_207352 (CYP4V2, cytochrome P450, family 4, subfamily V, polypeptide 2), gene registration number (Genebank) NM_002047 (GARS, glycyl-tRNA synthetase), gene registration number (Genebank) NM_003344 (UBE2H, ubiquitin-conjugating enzyme E2H UBC8 homolog, yeast)), Genebank NM_003729 (RTCD1, RNA terminal phosphate cyclase domain 1), Genebank NM_005358 (LMO7, LIM domain 7), Genebank NM_006292 (TSG101, tumor susceptibility gene 101), Genebank NM_032673 (PCGF1, polycomb group ring finger 1), Genebank NM_178532 (RNF180, ring finger protein 180), Genebank AF031469 (MR1, major histocompatibility complex, class I-re lated), Genebank BC029781 (C2, complement component 2), Genebank NM_000623 (BDKRB2, bradykinin receptor B2), Genebank NM_001065 (TNFRSF1A, tumor necrosis factor receptor superfamily, member 1A), Genebank NM_001838 (CCR7, chemokine (CC motif) receptor 7), Genebank (Genebank) NM_002119 (HLA-DOA, major histocompatibility complex, class II, DO alpha), Genebank (Genebank) ) NM_002184 (IL6ST, interleukin 6 signal transducer (gp130, oncostatin M receptor)), gene registration number (Genebank) NM_002259 (KLRC1, killer cell lectin-like receptor subfamily C, member 1), gene registration number (Genebank) NM_005018 (PDCD1 , programmed cell death 1), Genebank NM_006866 (LILRA2, leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 2), Genebank NM_014314 (DDX58, DEAD (Asp-Glu) -Ala-Asp) box polypeptide 58), gene registration number (G enebank) NM_016232 (IL1RL1, interleukin 1 receptor-like 1), gene accession number (Genebank) NM_018284 (GBP3, guanylate binding protein 3), gene accession number (Genebank) NM_021034 (IFITM3, interferon induced transmembrane protein 3 (1-8U) ), Gene registration number (Genebank) NM_031409 (CCR6, chemokine (CC motif) receptor 6), gene registration number (Genebank) NM_203330 (CD59, CD59 molecule, complement regulatory protein), gene registration number (Genebank) AF078165 (AXIN2, axin 2 (conductin, axil)), Genebank NM_000419 (ITGA2B, integrin, alpha 2b (platelet glycoprotein IIb of IIb / IIIa complex, antigen CD41)), Genebank NM_000758 (CSF2, colony stimulating factor 2 (granulocyte-macrophage)), Genebank (Genebank) NM_001124 (ADM, adrenomedullin), Genebank (Genebank) NM_001381 (DOK1, docking protein 1,62kDa (downstream of tyrosine kinase 1)), Genebank (Genebank) NM_002010 (FGF9, fibroblast growth factor 9 (glia-activating fac) tor)), Genebank NM_002088 (GRIK5, glutamate receptor, ionotropic, kainate 5), Genebank NM_002222 (ITPR1, inositol 1,4,5-triphosphate receptor, type 1), gene registry number (Genebank) NM_002224 (ITPR3, inositol 1,4,5-triphosphate receptor, Type 3), gene registration number (Genebank) NM_002350 (LYN, v-yes-1 Yamaguchi sarcoma viral related oncogene homolog), gene registration number (Genebank) NM_002561 (P2RX5, purinergic receptor P2X, ligand-gated ion channel, 5), gene registration number (Genebank) NM_003979 (GPRC5A, G protein-coupled receptor, family C, group 5, member A), gene registration number (Genebank) NM_004672 (MAP3K6, mitogen-activated protein kinase kinase kinase 6), gene registration number (Genebank) NM_004843 (IL27RA, interleukin 27 receptor, alpha), gene registration number (Genebank) NM_005297 (MCHR1, melanin-concentrating hormone receptor 1), gene Registration Number (Genebank) NM_022772 (EPS8L2, EPS8-like 2), Gene Registration Number (Genebank) NM_030 571 (NDFIP1, Nedd4 family interacting protein 1), Genebank NM_032174 (TOMM40L, translocase of outer mitochondrial membrane 40 homolog (yeast) -like), Genebank NM_058172 (ANTXR2, anthrax toxin receptor 2) , Gene Registration Number (Genebank) NM_153002 (GPR156, G protein-coupled receptor 156), Gene Registration Number (Genebank) NM_181501 (ITGA1, integrin, alpha 1), Gene Registration Number (Genebank) NM_182665 (RASSF5, Ras association (RalGDS / AF-6) domain family 5), genebank (Genebank) AB210045 (KIF5A, kinesin family member 5A), genebank (Genebank) BC010091 (BICD1, bicaudal D homolog 1 (Drosophila)), genebank (Genebank) BC027875 (MYO15B, myosin XVB pseudogene), Gene Registration Number (Genebank) NM_002213 (ITGB5, integrin, Beta 5), Gene Registration Number (Genebank) NM_004735 (LRRFIP1, leucine rich repeat (in FLII) interacting protein 1), Gene Registration Number Genebank NM_005231 (CTTN, cortactin), Gene Registration Number (Genebank) ) NM_005507 (CFL1, cofilin 1 (non-muscle)), Gene Registration Number (Genebank) NM_006091 (CORO2B, coronin, actin binding protein, 2B), Gene Registration Number (Genebank) NM_006380 (APPBP2, amyloid beta precursor protein (cytoplasmic tail) ) binding protein 2), gene registration number (Genebank) NM_012144 (DNAI1, dynein, axonemal, intermediate chain 1), gene registration number (Genebank) NM_015990 (KLHL5, kelch-like 5 (Drosophila)), gene registration number (Genebank) NM_018222 (PARVA, parvin, alpha), Gene Registration Number (Genebank) NM_021109 (TMSB4X, thymosin, beta 4, X-linked), Gene Registration Number (Genebank) NM_022765 (MICAL1, microtubule associated monoxygenase, calponin and LIM domain containing 1) , Gene Registration Number (Genebank) NM_031308 (EPPK1, epiplakin 1), Gene Registration Number (Genebank) NM_033375 (MYO1C, myosin IC), Gene Registration Number (Genebank) NM_080881 (DBN1, drebrin 1), Gene Registration Number (Genebank) NM_152237 (GAS2L1, growth arrest-specific 2 like 1), Genebank NM _213636 (PDLIM7, PDZ and LIM domain 7 (enigma)), Gene Registration Number (Genebank) NM_000021 (PSEN1, presenilin 1 (Alzheimer disease 3)), Gene Registration Number (Genebank) NM_002034 (FUT5, fucosyltransferase 5 (alpha (1, Fucosyltransferase), Genebank NM_002046 (GAPDH, glyceraldehyde-3-phosphate dehydrogenase), Genebank NM_002392 (MDM2, Mdm2, transformed 3T3 cell double minute 2, p53 binding protein (mouse)) , Gene Registration Number (Genebank) NM_003333 (UBA52, ubiquitin A-52 residue ribosomal protein fusion product 1), Gene Registration Number (Genebank) NM_004505 (USP6, ubiquitin specific peptidase 6 (Tre-2 oncogene)), Gene Registration Number (Genebank) ) NM_005805 (PSMD14, proteasome (prosome, macropain) 26S subunit, non-ATPase, 14), Gene Registration Number (Genebank) NM_013396 (USP25, ubiquitin specific peptidase 25), Gene Registration Number (Genebank) NM_017584 (MIOX, myo-inositol oxygenase), Genebank NM_021009 (UBC, ubiquitin C), heredity Genebank NM_032582 (USP32, ubiquitin specific peptidase 32), Gene Registry Number (Genebank) NM_033500 (HK1, hexokinase 1), Gene Registration Number (Genebank) NM_001310 (CREBL2, cAMP responsive element binding protein-like 2), Genebank NM_002166 (ID2, inhibitor of DNA binding 2, dominant negative helix-loop-helix protein), Genebank NM_002622 (PFDN1, prefoldin subunit 1), Genebank NM_003113 (SP100 , SP100 nuclear antigen), Genebank NM_005419 (STAT2, signal transducer and activator of transcription 2, 113kDa), Genebank NM_005526 (HSF1, heat shock transcription factor 1), Genebank (Genebank) NM_005920 (MEF2D, myocyte enhancer factor 2D), gene registration number (Genebank) NM_014212 (HOXC11, homeobox C11), gene registration number (Genebank) NM_014423 (AFF4, AF4 / FMR2 family, member 4), gene registration number (Genebank) NM_015106 (RAD54L2, RAD54-like 2 (S. cerevisiae)), gene registration number (Genebank) NM_017422 (CALML5, calmodulin-like 5), gene registration number (Genebank) NM_032292 (GON4L, gon-4-like (C. elegans)), gene registration number (Genebank) NM_134424 ( RAD52, RAD52 homolog (S. cerevisiae)), gene registration number (Genebank) NM_144631 (ZNF513, zinc finger protein 513), gene registration number (Genebank) NM_001012334 (MDK, midkine (neurite growth-promoting factor 2)), gene registration Number (Genebank) NM_001761 (CCNF, cyclin F), Gene Registration Number (Genebank) NM_001789 (CDC25A, cell division cycle 25 homolog A (S. pombe), Gene Registration Number (Genebank) NM_002823 (PTMA, prothymosin, alpha (gene) sequence 28)), gene registration number (Genebank) NM_007295 (BRCA1, Breast cancer 1, early onset), gene registration number (Genebank) NM_014221 (MTCP1, mature T-cell proliferation 1), gene registration number (Genebank) NM_014708 (KNTC1 , kinetochore associated 1), Genebank NM_015097 (CLASP2, cytoplasmic linker associated protein 2), heredity Registration Number (Genebank) NM_018151 (RIF1, RAP1 interacting factor homolog (yeast)), gene registration number (Genebank) AL117645 (MED28, mediator of RNA polymerase II transcription, subunit 28 homolog (S. cerevisiae)), Genebank BC042297 (UBTF, upstream binding transcription factor, RNA polymerase I), Genebank NM_000449 (RFX5, regulatory factor X, 5 (influences HLA class II expression)), gene registration Number (Genebank) NM_001032372 (ZNF226, zinc finger protein 226), gene registration number (Genebank) NM_003216 (TEF, thyrotrophic embryonic factor), gene registration number (Genebank) NM_003411 (ZFY, zinc finger protein, Y-linked), gene registration Number (Genebank) NM_003865 (HESX1, HESX homeobox 1), Gene Registration Number (Genebank) NM_003920 (TIMELESS, timeless homolog (Drosophila)), Gene Registration Number (Genebank) NM_005254 (GABPB2, GA binding protein transcription factor, beta subunit 2) , Gene Registration Number (Genebank) NM_006089 (SCML2, sex comb on midleg-like 2 (Drosophila)), Gene Registration Number (Genebank) NM_006454 (MXD4, MAX dimerization protein 4), Gene Registration Number (Genebank) NM_006530 (YEATS4, YEATS domain containing 4), gene registration Genebank NM_013249 (ZNF214, zinc finger protein 214), Genebank NM_014288 (ITGB3BP, integrin beta 3 binding protein (beta3-endonexin)), Genebank NM_016578 (RSF1, remodeling and spacing factor 1), Gene Registration Number (Genebank) NM_018645 (HES6, hairy and enhancer of split 6 (Drosophila)), Gene Registration Number (Genebank) NM_020062 (SLC2A4RG, SLC2A4 regulator), Gene Registration Number (Genebank) NM_021148 (ZNF273, zinc finger protein 273), Genebank NM_021269 (ZNF708, zinc finger protein 708), Genebank NM_025027 (ZNF606, zinc finger protein 606), Genebank NM_144566 (ZNF700, zinc finger protein 700 Genebank (Genebank) NM_175910 (ZNF493, zinc finger protein 493), Genebank (Genebank) NM_198968 (DZIP1, DAZ interacting protein 1), Genebank Y09321 (TAF4B, TAF4b RNA polymerase II, TATA) box binding protein (TBP) -associated factor, 10 5 kDa), Genebank NM_000251 (MSH2, mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)), Genebank NM_001039651 (C6orf26, chromosome 6 open reading frame 26), Genebank NM_001071 (TYMS, thymidylate synthetase), Genebank NM_002485 (NBN, nibrin), Gene Genebank NM_002592 (PCNA, proliferating cell nuclear antigen), Genebank NM_004219 (PTTG1, pituitary tumor-transforming 1), Genebank NM_005427 (TP73, tumor protein p73), gene registry number (Genebank) NM_005441 (CHAF1B, chromatin assembly factor 1, subunit B (p60)), gene registration number (Genebank) NM_005484 (PARP2, poly (ADP-ribose) polymerase family, member 2), gene registration number (Genebank) NM_016218 ( POLK, polymerase (DNA directed) kappa), genebank (Genebank) BC048985 (TAF15, TAF15 RNA polymerase II, TATA box binding protein (TBP) -associated factor, 68kDa), genebank (Genebank) NM_001007101 (ZNF484, zinc finger protein 484, Genebank NM_002383 (M AZ, MYC-associated zinc finger protein (purine-binding transcription factor), Genebank NM_003316 (TTC3, Tetratricopeptide repeat domain 3), Genebank NM_003410 (ZFX, zinc finger protein, X-linked ), Gene registration number (Genebank) NM_005060 (RORC, RAR-related orphan receptor C), gene registration number (Genebank) NM_006963 (ZNF22, zinc finger protein 22 (KOX 15)), gene registration number (Genebank) NM_014898 (ZFP30, zinc finger protein 30 homolog (mouse), Genebank NM_016019 (LUC7L2, LUC7-like 2 (S. cerevisiae)), Gene Registration Number (Genebank) NM_017661 (SUHW4, suppressor of hairy wing homolog 4 (Drosophila)), Gene Registration Number (Genebank) NM_021178 (CCNB1IP1, cyclin B1 interacting protein 1), Gene Registration Number (Genebank) NM_030899 ( ZNF323, zinc finger protein 323), Genebank NM_032268 (ZNRF1, zinc and ring finger 1), Genebank NM_033089 (ZCCHC3, zinc finger, cCHC domain containing 3), Genebank (Genebank) ) NM_152355 (ZNF441, zinc finger protein 441), Genebank (Genebank) NM_181756 (ZNF233, zinc finger protein 233), Genebank (Genebank) NM_182515 (ZNF714, zinc finger protein 714), Genebank (Kenebank) AK131529 (AATK, apoptosis-associated tyrosine kinase), gene registration number (Genebank) NM_000289 (PFKM, phosphofructokinase, Muscle), gene registration number (Genebank) NM_000553 (WRN, Werner syndrome), gene registration number (Genebank) NM_001786 (CDC2, cell division cycle 2, g1 to S and G2 to M), Gene Registration Number (Genebank) NM_001813 (CENPE, centromere protein E, 312 kDa), Gene Registration Number (Genebank) NM_003579 (RAD54L, RAD54-like (S. cerevisiae)), Gene Registration Number (Genebank) NM_005964 (MYH10, Myosin, heavy chain 10, non-muscle), gene registration number (Genebank) NM_006306 (SMC1A, structural maintenance of chromosomes 1A), gene registration number (Genebank) NM_013257 (SGK3, serum / glucocorticoid regulated kinase family, Member 3), gene registration number ( Genebank) NM_014616 (ATP11B, aTPase, class VI, Type 11B), Gene Registration Number (Genebank) NM_015512 (DNAH1, dynein, axonemal, heavy chain 1), Gene Registration Number (Genebank) NM_016350 (NIN, ninein (GSK3B interacting protein) Genebank NM_018183 (SBNO1, strawberry notch homolog 1 (Drosophila)), Genebank NM_020159 (SMARCAD1, sWI / SNF-related, Matrix-associated actin-dependent regulator of chromatin, subfamily a, containing DEAD / H box 1), Gene Accession Number (Genebank) NM_024320 (ATAD 4, aTPase family, aAA domain containing 4), Genebank NM_024594 (PANK3, pantothenate kinase 3), Genebank NM_033151 (ABCC11, aTP-binding cassette, sub-family C (CFTR / MRP) , Member 11), Gene Registration Number (Genebank) NM_182802 (MCM8, Minichromosome maintenance complex component 8), Gene Registration Number (Genebank) NM_207578 (PRKACB, protein kinase, cAMP-dependent, catalytic, Beta), Gene Registration Number (Genebank) NR_002451 (ABCA11, aTP-binding cassette, sub-family A (ABC1), Member 11 (pseudogene)), gene registration number (Genebank) AF042838 (MAP3K1, Mitogen-activated protein kinase kinase kinase 1), gene registration number (Genebank) AL117400 (PASK, pAS domain containing serine / threonine kinase), gene accession number (Genebank) NM_000221 (KHK, ketohexokinase (fructokinase)), gene accession number (Genebank) NM_001005735 (CHEK2, cHK2 checkpoint homolog (S. pombe), Genebank NM_001626 (AKT2, v-akt murine thymoma viral oncogene homolog 2), Genebank NM_001826 (CKS1B, cDC28 protein kinase regulatory subunit 1B), Genebank NM_002758 (MAP2K6, Mitogen-activated protein kinase kinase 6), gene registration number (Genebank) NM_005400 (PRKCE, protein kinase C, epsilon), gene registration number (Genebank) NM_006716 (DBF4, dBF4 homolog (S. cerevisiae)), gene registration Genebank NM_014215 (insrr, insulin receptor-related receptor), Genebank NM_023110 (FGFR1, fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, pfeiffer syndrome), Genebank NM_032246 (RKHD3, Ring finger and KH domain containing 3), Genebank (Genebank) NM_052987 (CDK10, cyclin-dependent kinase (CDC2-like) 10), Gene Registry (Genebank) NM_001005526 (SF3B1, splicing factor 3b, subunit 1,155 kDa), Gene Registration Number (Genebank) NM_002138 (HNRPD , heterogeneous nuclear ribonucleoprotein D (AU-rich element RNA binding protein 1,37kDa), gene registration number (Genebank) NM_003400 (XPO1, exportin 1 (CRM1 homolog, Yeast)), gene registration number (Genebank) NM_004814 (WDR57, WD repeat domain 57 (U5 snRNP specific), Genebank NM_005033 (EXOSC9, exosome component 9), Genebank NM_006527 (SLBP, stem-loop (histone) binding protein), Genebank (Genebank) ) NM_006638 (RPP40, Ribonuclease P 40kDa subunit), gene registration number (Genebank) NM_006805 (HNRPA0, heterogeneous nuclear ribonucleoprotein A0), gene registration number (Genebank) NM_014953 (DIS3, dIS3 mitotic control homolog (S. cerevisiae)), gene registration number (Genebank) NM_032361 (THOC3, THO complex 3), gene registration number (Genebank) NM_152292 (RG9MTD2, RNA (guanine-9-) methyltransferase domain containing 2), gene registration number (Genebank) AF090937 ( SORBS2, sorbin and SH3 domain containing 2), Genebank NM_000583 (GC, group-specific component (vitamin D binding protein)), Genebank NM_001001290 (SLC2A9, solute carrier family 2 (facilitated glucose transporter) ), Member 9), Genebank NM_001045 (SLC6A4, solute carrier family 6 (neurotransmitter transporter, serotonin, Member 4), Genebank NM_003366 (UQCRC2, ubiquinol-cytochrome c reductase core protein II), Genebank NM_004896 (VPS26A, vacuolar protein sorting 26 homolog A (S.pombe)), Genebank number (Genebank) NM_006028 (HTR3B, 5-hydroxytryptamine (serotonin) receptor 3B), Genebank number NM_006359 (SLC9A6, solute carrier family 9 (s odium / hydrogen exchanger), Member 6), Genebank NM_006416 (SLC35A1, solute carrier family 35 (CMP-sialic acid transporter), Member A1), Genebank NM_006544 (EXOC5, exocyst complex component 5 ), Gene registration number (Genebank) NM_014229 (SLC6A11, solute carrier family 6 (neurotransmitter transporter, gABA), Member 11), gene registration number (Genebank) NM_016057 (COPZ1, coatomer protein complex, subunit zeta 1), gene registration number ( Genebank) NM_016320 (NUP98, nucleoporin 98kDa), Genebank Number (Genebank) NM_018155 (SLC25A36, solute carrier family 25, Member 36), Genebank Number (Genebank) NM_175623 (RAB3IP, RAB3A interacting protein (rabin3), Gene Registration Number (Genebank) AF256215 (ARNTL2, aryl hydrocarbon receptor nuclear translocator-like 2), gene accession number (Genebank) BC041387 (MCTP2, Multiple C2 domains, Transmembrane 2), gene accession number (Genebank) NM_000506 (F2, coagulation factor II (thrombin) )), Gene Registration Number (Genebank) NM_000820 (GAS6, growth arrest-specific 6), Gene Registration Number (Genebank) NM_002317 (LOX, Lysyl oxidase), Gene Registration Number (Genebank) NM_002834 (PTPN11, protein tyrosine phosphatase, non-receptor type 11 (Noonan) syndrome 1)), gene registration number (Genebank) NM_003546 (HIST1H4L, histone cluster 1, h4l), gene registration number (Genebank) NM_004311 (ARL3, aDP-ribosylation factor-like 3), gene registration number (Genebank) NM_006203 (PDE4D , phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, drosophila), Genebank NM_012096 (APPL1, adapter protein, phosphotyrosine interaction, pH domain and leucine zipper containing 1), Genebank NM_012309 ( SHANK2, sH3 and multiple ankyrin repeat domains 2), Genebank NM_012425 (RSU1, Ras suppressor protein 1), Genebank NM_015547 (ACOT11, acyl-CoA thioesterase 11), Genebank (Genebank) NM_016022 (APH1A, anterior pharynx defec tive 1 homolog A (C. elegans)), Genebank NM_024718 (C9orf86, chromosome 9 open reading frame 86), Genebank NM_080651 (THRAP6, Thyroid hormone receptor associated protein 6), Genebank NM_181523 (PIK3R1, phosphoinositide-3-kinase, Regulatory subunit 1 (p85 alpha)), gene accession number (Genebank) NM_194455 (KRIT1, KRIT1, ankyrin repeat containing), gene accession number (Genebank) NM_002089 (CXCL2, chemokine (CXC motif) ligand 2) , Genebank (Genebank) NM_003810 (TNFSF10, Tumor necrosis factor (ligand) superfamily, Member 10), Genebank (Genebank) NM_003811 (TNFSF9, Tumor necrosis factor (ligand) superfamily, Member 9), Gene accession number (Genebank) ) NM_031479 (INHBE, inhibin, beta E), Gene Registration Number (Genebank) NM_017915 (C12orf48, chromosome 12 open reading frame 48), Gene Registration Number (Genebank) BC021267 (KLHL14, kelch-like 14 (Drosophila))

1) Among the biomarkers, biomarker genes whose expression is increased by exposure of indeno (1,2,3-c, d) pyrene are as follows:

Genebank (Genebank) NM_000606 (C8G, complement component 8, gamma polypeptide), Genebank (Genebank) NM_001429 (EP300, e1A binding protein p300), Genebank (Menebank) NM_003804 (RIPK1, Receptor (TNFRSF) -interacting serine-threonine kinase 1), Genebank NM_003806 (HRK, harakiri, BCL2 interacting protein (contains only BH3 domain)), Genebank NM_003901 (SGPL1, sphingosine-1-phosphate lyase 1), Gene Registration Number (Genebank) NM_004049 (BCL2A1, BCL2-related protein A1), Gene Registration Number (Genebank) NM_006437 (PARP4, poly (ADP-ribose) polymerase family, member 4), Gene Registration Number (Genebank) NM_020371 (AVEN, apoptosis , caspase activation inhibitor), genebank NM_022094 (CIDEC, cell death-inducing DFFA-like effector c), genebank NM_022151 (MOAP1, Modulator of apoptosis 1), genebank NM_133369 (UNC5A, unc-5 homolog A (C. Elegans)), genes, etc. (Genebank) NM_138578 (BCL2L1, BCL2-like 1), Gene Registration Number (Genebank) AB040944 (ZSWIM5, zinc finger, sWIM-type containing 5), Gene Registration Number (Genebank) AF144233 (ZMYND8, zinc finger, MYND- type containing 8), gene registration number (Genebank) NM_000176 (NR3C1, nuclear receptor subfamily 3, group C, Member 1 (glucocorticoid receptor)), gene registration number (Genebank) NM_002180 (IGHMBP2, immunoglobulin mu binding protein 2), gene registration Number (Genebank) NM_006254 (PRKCD, protein kinase c, delta), gene registration number (Genebank) NM_016213 (TRIP4, Thyroid hormone receptor interactor 4), gene registration number (Genebank) NM_019062 (RNF186, Ring finger protein 186), gene registration Genebank NM_022482 (GZF1, gDNF-inducible zinc finger protein 1), Gene Registration Number (Genebank) NM_033092 (TRIM5, Tripartite motif-containing 5), Genebank Number NM_138287 (DTX3L, deltex 3-like (Drosophila) ), Gene Registration Number (Genebank) NM_145288 (ZNF342, zinc finger prot ein 342), Genebank NM_173548 (ZNF584, zinc finger protein 584), Genebank XM_930521 (ZNF506, zinc finger protein 506), Genebank BX648244 (SPATA13, spermatogenesis associated 13) , Gene Registration Number (Genebank) CR599277 (SERPINB2, serpin peptidase inhibitor, clade B (ovalbumin), Member 2), Gene Registration Number (Genebank) NM_000308 (CTSA, cathepsin A), Gene Registration Number (Genebank) NM_001002857 (ANXA2, annexin A2), gene registration number (Genebank) NM_001320 (CSNK2B, casein kinase 2, Beta polypeptide), gene registration number (Genebank) NM_001750 (CAST, calpastatin), gene registration number (Genebank) NM_004152 (OAZ1, ornithine decarboxylase antizyme 1) , Gene Registration Number (Genebank) NM_006869 (CENTA1, centaurin, alpha 1), Gene Registration Number (Genebank) NM_014889 (PITRM1, pitrilysin metallopeptidase 1), Gene Registration Number (Genebank) NM_014916 (LMTK2, Lemur tyrosine kinase 2) Number (Genebank) NM_015941 (AT P6V1H, aTPase, h + transporting, Lysosomal 50 / 57kDa, v1 subunit H), Genebank NM_018482 (DDEF1, development and differentiation enhancing factor 1), Genebank NM_018993 (RIN2, Ras and Rab interactor 2), gene registration number (Genebank) NM_032258 (TBC1D3, TBC1 domain family, Member 3), gene registration number (Genebank) NM_058197 (CDKN2A, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)), gene registration number (Genebank) NM_198681 (PLEKHG5, pleckstrin homology domain containing, family G (with RhoGef domain) member 5), Genebank BC002828 (AGGF1, angiogenic factor with G patch and FHA domains 1), Genebank (Genebank) NM_000875 (IGF1R, insulin-like growth factor 1 receptor), genebank (Genebank) NM_001562 (IL18, interleukin 18 (interferon-gamma-inducing factor)), genebank (Genebank) NM_002831 (PTPN6, protein tyrosine phosphatase, non receptor type 6), gene registration number (Geneban) k) NM_003999 (OSMR, oncostatin M receptor), Genebank NM_004624 (VIPR1, vasoactive intestinal peptide receptor 1), Genebank NM_005557 (KRT16, keratin 16 (focal non-epidermolytic palmoplantar keratoderma), Genebank (Genebank) NM_005755 (EBI3, epstein-Barr virus induced gene 3), Genebank (Genebank) NM_007063 (TBC1D8, TBC1 domain family, member 8 (with GRAM domain)), Genebank (Genebank) NM_016558 ( SCAND1, sCAN domain containing 1), Genebank NM_032965 (CCL15, chemokine (CC motif) ligand 15), Genebank AF343007 (FOXC1, forkhead box C1), Genebank AK074757 (Genebank) ZNF253, zinc finger protein 253), genebank BC063666 (CREB3L2, cAMP responsive element binding protein 3-like 2), genebank NM_001010926 (HES5, hairy and enhancer of split 5 (Drosophila)), Genebank NM_002167 (ID3, inhibitor of DN A binding 3, dominant negative helix-loop-helix protein), Genebank NM_002501 (NFIX, nuclear factor I / X (CCAAT-binding transcription factor)), Genebank NM_003107 (SOX4, sRY ( sex determining region Y) -box 4), Genebank NM_003475 (RASSF7, Ras association (RalGDS / AF-6) domain family 7), Genebank NM_005315 (GSCL, goosecoid-like), Gene Genebank NM_005848 (DENND4A, dENN / MADD domain containing 4A), Genebank NM_005902 (SMAD3, sMAD family member 3), Genebank NM_006663 (PPP1R13L, protein phosphatase 1, Regulatory (inhibitor) subunit 13 like), Genebank NM_007005 (TLE4, Transducin-like enhancer of split 4 (E (sp1) homolog, Drosophila)), Genebank NM_012240 (SIRT4, sirtuin (silent mating type information) regulation 2 homolog) 4 (S. cerevisiae)), Genebank NM_014368 (LHX6, LIM homeobox 6), Genebank NM_015481 (ZNF385, zinc finger protein 385), Genebank NM_016170 (TLX2, T-cell leukemia homeobox 2), gene registration number (Genebank) NM_021961 (TEAD1, TEA domain family member 1 (SV40 transcriptional enhancer factor)), gene registration number (Genebank) NM_130439 (MXI1, MAX interactor 1), gene registration number (Genebank) NM_152287 (ZNF276 , zinc finger protein 276), gene accession number (Genebank) NM_207305 (FOXD4, forkhead box D4), gene accession number (Genebank) BC035714 (CYP19A1, cytochrome P450, family 19, subfamily A, polypeptide 1), gene accession number (Genebank) ) NM_000603 (NOS3, nitric oxide synthase 3 (endothelial cell)), gene registration number (Genebank) NM_000761 (CYP1A2, cytochrome P450, family 1, subfamily A, polypeptide 2), gene registration number (Genebank) NM_001013660 (FRRS1, ferric- chelate reductase 1), gene accession number (Genebank) NM_004542 (ND UFA3, nADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 3,9kDa), gene registration number (Genebank) NM_005390 (PDHA2, pyruvate dehydrogenase (lipoamide) alpha 2), gene registration number (Genebank) NM_005625 (SDCBP, syndecan binding protein (syntenin) )), Gene Registration Number (Genebank) NM_006157 (NELL1, nEL-like 1 (chicken)), Gene Registration Number (Genebank) NM_017460 (CYP3A4, cytochrome P450, family 3, subfamily A, polypeptide 4), Gene Registration Number ( Genebank) NM_019885 (CYP26B1, cytochrome P450, family 26, subfamily B, polypeptide 1), Genebank NM_022051 (EGLN1, egl nine homolog 1 (C. elegans)), gene registration number (Genebank) NM_032783 (CBR4, carbonyl reductase 4), gene registration number (Genebank) NM_145690 (YWHAZ, Tyrosine 3-monooxygenase / tryptophan 5-monooxygenase activation protein, zeta polypeptide), gene registration number (Genebank) ) NM_207352 (CYP4V2, cytochrome P450, family 4, subfamily V, polypeptide 2), gene registration number (Genebank) NM_002047 (GARS, glycyl-tRNA synthetase), gene registration number (Genebank) NM_003344 (UBE2H, ubiquitin-conjugating enzyme E2H UBC8 homolog, yeast)), Genebank NM_003729 (RTCD1, RNA terminal phosphate cyclase domain 1), Genebank NM_005358 (LMO7, LIM domain 7), Genebank NM_006292 (TSG101, Tumor susceptibility gene 101), Genebank NM_032673 (PCGF1, polycomb group ring finger 1), Genebank NM_178532 (RNF180, Ring finger protein 180), Genebank AF031469 (MR1, Major histocompatibility complex, class I-rel ated), Genebank BC029781 (C2, complement component 2), Genebank NM_000623 (BDKRB2, Bradykinin receptor B2), Genebank NM_001065 (TNFRSF1A, Tumor necrosis factor receptor superfamily, Member 1A), Genebank NM_001838 (CCR7, chemokine (CC motif) receptor 7), Genebank (Genebank) NM_002119 (HLA-DOA, Major histocompatibility complex, class II, dO alpha), Genebank (Genebank) ) NM_002184 (IL6ST, interleukin 6 signal transducer (gp130, oncostatin M receptor)), gene registration number (Genebank) NM_002259 (KLRC1, killer cell lectin-like receptor subfamily C, Member 1), gene registration number (Genebank) NM_005018 (PDCD1 , programmed cell death 1), Genebank NM_006866 (LILRA2, Leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 2), Genebank NM_014314 (DDX58, dEAD (Asp-Glu -Ala-Asp) box polypeptide 58), gene registration number (Ge nebank) NM_016232 (IL1RL1, interleukin 1 receptor-like 1), gene accession number (Genebank) NM_018284 (GBP3, guanylate binding protein 3), gene accession number (Genebank) NM_021034 (IFITM3, interferon induced transmembrane protein 3 (1-8U) ), Gene registration number (Genebank) NM_031409 (CCR6, chemokine (CC motif) receptor 6), gene registration number (Genebank) NM_203330 (CD59, cD59 molecule, complement regulatory protein), gene registration number (Genebank) AF078165 (AXIN2, axin 2 (conductin, axil)), Genebank NM_000419 (ITGA2B, integrin, alpha 2b (platelet glycoprotein IIb of IIb / IIIa complex, antigen CD41)), Genebank NM_000758 (CSF2, colony stimulating factor 2 (granulocyte-macrophage)), Genebank (Genebank) NM_001124 (ADM, adrenomedullin), Genebank (Genebank) NM_001381 (DOK1, docking protein 1,62kDa (downstream of tyrosine kinase 1)), Genebank (Genebank) NM_002010 (FGF9, fibroblast growth factor 9 (glia-activating facto r)), Genebank NM_002088 (GRIK5, glutamate receptor, ionotropic, kainate 5), Genebank NM_002222 (ITPR1, inositol 1,4, 5-triphosphate receptor, Type 1), gene registry number (Genebank) NM_002224 (ITPR3, inositol 1,4, 5-triphosphate receptor, Type 3), gene registration number (Genebank) NM_002350 (LYN, v-yes-1 Yamaguchi sarcoma viral related oncogene homolog), gene registration number (Genebank) NM_002561 (P2RX5, purinergic receptor P2X, Ligand-gated ion channel, 5), gene registration number (Genebank) NM_003979 (GPRC5A, g protein-coupled receptor, family C, group 5, Member A), gene registration number (Genebank) NM_004672 (MAP3K6, Mitogen-activated protein kinase kinase kinase 6), gene registration number (Genebank) NM_004843 (IL27RA, interleukin 27 receptor, alpha), gene registration number (Genebank) NM_005297 (MCHR1, Melanin-concentrating hormone receptor 1), gene registration Number (Genebank) NM_022772 (EPS8L2, ePS8-like 2), Gene Registration Number (Genebank) NM_0305 71 (NDFIP1, nedd4 family interacting protein 1), Genebank NM_032174 (TOMM40L, Translocase of outer mitochondrial membrane 40 homolog (yeast) -like), Genebank NM_058172 (ANTXR2, anthrax toxin receptor 2) , Genebank NM_153002 (GPR156, g protein-coupled receptor 156), Genebank NM_181501 (ITGA1, integrin, alpha 1), Genebank NM_182665 (RASSF5, Ras association (RalGDS / AF-6) domain family 5), Genebank AB210045 (KIF5A, kinesin family member 5A), Genebank BC010091 (BICD1, Bicaudal D homolog 1 (Drosophila)), Genebank (Genebank) BC027875 (MYO15B, Myosin XVB pseudogene), Gene Registration Number (Genebank) NM_002213 (ITGB5, integrin, Beta 5), Gene Registration Number (Genebank) NM_004735 (LRRFIP1, Leucine rich repeat (in FLII) interacting protein 1), Gene Registration Number Genebank NM_005231 (CTTN, cortactin), Gene Registration Number (Genebank) ) NM_005507 (CFL1, cofilin 1 (non-muscle)), Gene Registration Number (Genebank) NM_006091 (CORO2B, coronin, actin binding protein, 2B), Gene Registration Number (Genebank) NM_006380 (APPBP2, amyloid beta precursor protein (cytoplasmic tail) ) binding protein 2), gene registration number (Genebank) NM_012144 (DNAI1, dynein, axonemal, intermediate chain 1), gene registration number (Genebank) NM_015990 (KLHL5, kelch-like 5 (Drosophila)), gene registration number (Genebank) NM_018222 (PARVA, parvin, alpha), Gene Registration Number (Genebank) NM_021109 (TMSB4X, Thymosin, Beta 4, X-linked), Gene Registration Number (Genebank) NM_022765 (MICAL1, Microtubule associated monoxygenase, calponin and LIM domain containing 1) , Gene Registration Number (Genebank) NM_031308 (EPPK1, epiplakin 1), Gene Registration Number (Genebank) NM_033375 (MYO1C, Myosin IC), Gene Registration Number (Genebank) NM_080881 (DBN1, drebrin 1), Gene Registration Number (Genebank) NM_152237 (GAS2L1, growth arrest-specific 2 like 1), Genebank NM_21 3636 (PDLIM7, pDZ and LIM domain 7 (enigma)), gene registration number (Genebank) NM_000021 (PSEN1, presenilin 1 (Alzheimer disease 3)), gene registration number (Genebank) NM_002034 (FUT5, fucosyltransferase 5 (alpha (1, 3) fucosyltransferase)), Genebank NM_002046 (GAPDH, glyceraldehyde-3-phosphate dehydrogenase), Genebank NM_002392 (MDM2, Mdm2, Transformed 3T3 cell double minute 2, p53 binding protein (mouse)) , Gene Registration Number (Genebank) NM_003333 (UBA52, ubiquitin A-52 residue ribosomal protein fusion product 1), Gene Registration Number (Genebank) NM_004505 (USP6, ubiquitin specific peptidase 6 (Tre-2 oncogene)), Gene Registration Number (Genebank) ) NM_005805 (PSMD14, proteasome (prosome, Macropain) 26S subunit, non-ATPase, 14), Gene Registration Number (Genebank) NM_013396 (USP25, ubiquitin specific peptidase 25), Gene Registration Number (Genebank) NM_017584 (MIOX, Myo-inositol oxygenase), Genebank NM_021009 (UBC, ubiquitin C), gene Genebank NM_032582 (USP32, ubiquitin specific peptidase 32), Gene Registration Number (Genebank) NM_033500 (HK1, hexokinase 1), Gene Registration Number (Genebank) NM_001310 (CREBL2, cAMP responsive element binding protein-like 2), Gene Genebank NM_002166 (ID2, inhibitor of DNA binding 2, dominant negative helix-loop-helix protein), Genebank NM_002622 (PFDN1, prefoldin subunit 1), Genebank NM_003113 (SP100, sP100 nuclear antigen, Genebank NM_005419 (STAT2, signal transducer and activator of transcription 2,113kDa), Genebank NM_005526 (HSF1, heat shock transcription factor 1), Genebank NM_005920 ( MEF2D, Myocyte enhancer factor 2D, Genebank NM_014212 (HOXC11, homeobox C11), Genebank NM_014423 (AFF4, aF4 / FMR2 family, Member 4), Genebank NM_015106 (RAD54L2 , RAD54-like 2 (S. cerevisiae)), gene registration number (Genebank) NM_017422 (CALML5, calmodulin-like 5), gene registration number (Genebank) NM_032292 (GON4L, gon-4-like (C. elegans)), gene registration number (Genebank) NM_134424 ( RAD52, RAD52 homolog (S. cerevisiae), Genebank NM_144631 (ZNF513, zinc finger protein 513)

2) Among the biomarkers, biomarker genes whose expression is reduced by exposure of indeno (1,2,3-c, d) pyrene are as follows:

Genebank (Genebank) NM_001012334 (MDK, Midkine (neurite growth-promoting factor 2), Genebank (Nene) NM_001761 (CCNF, cyclin F), Genebank (Menebank) NM_001789 (CDC25A, cell division cycle 25 homolog A (S. pombe)), Genebank NM_002823 (PTMA, prothymosin, alpha (gene sequence 28)), Genebank NM_007295 (BRCA1, Breast cancer 1, early onset), Gene accession number ( Genebank) NM_014221 (MTCP1, Mature T-cell proliferation 1), Genebank NM_014708 (KNTC1, kinetochore associated 1), Genebank NM_015097 (CLASP2, cytoplasmic linker associated protein 2), Gene accession number ( Genebank) NM_018151 (RIF1, RAP1 interacting factor homolog (yeast), Genebank AL117645 (MED28, Mediator of RNA polymerase II transcription, subunit 28 homolog (S. cerevisiae)), Gene accession number (Genebank) BC042297 ( UBTF, upstream binding transcription factor, RNA polymerase I), Genebank NM_000449 (RFX5, Regulatory factor X, 5 (influences HLA class II expression)), Genebank NM_001032372 (ZNF226, zinc finger protein 226), Genebank NM_003216 (TEF, Thyrotrophic embryonic factor, Genebank NM_003411 (ZFY, zinc finger protein, Y-linked), Genebank NM_003865 (HESX1, hESX homeobox 1), Genebank NM_003920 (TIMELESS, Timeless homolog (Drosophila), Genebank NM_005254 (GABPB2, gA binding protein transcription factor, Beta subunit 2), Genebank NM_006089 (SCML2, sex comb on midleg-like 2 (Drosophila)), gene Genebank NM_006454 (MXD4, MAX dimerization protein 4), Genebank NM_006530 (YEATS4, YEATS domain containing 4), Genebank NM_013249 (ZNF214, zinc finger protein 214), Gene Registration Number (Genebank) NM_014288 (ITGB3BP, integrin beta 3 binding protein (beta3-endonexin)), genebank NM_016578 (RSF1, Remodeling and spacing factor 1), genebank NM_018645 (HES6, hairy and enhancer of split 6 (Drosophila)), gene registration Number (Genebank) NM_020062 (SLC2A4RG, sLC2A4 regulator), Gene Registration Number (Genebank) NM_021148 (ZNF273, zinc finger protein 273), Gene Registration Number (Genebank) NM_021269 (ZNF708, zinc finger protein 708), Gene Registration Number (Genebank) NM_025027 (ZNF606, zinc finger protein 606), Genebank NM_144566 (ZNF700, zinc finger protein 700), Genebank NM_175910 (ZNF493, zinc finger protein 493), Gene accession number (Genebank) NM_198968 (Genebank) DZIP1, dAZ interacting protein 1), Genebank Y09321 (TAF4B, TAF4b RNA polymerase II, TATA box binding protein (TBP) -associated factor, 105kDa), Genebank (Menebank) NM_000251 (MSH2, MutS homolog 2 , colon cancer, nonpolyposis type 1 (E. coli)), Genebank NM_001039651 (C6orf26, chromosome 6 open reading frame 26), Genebank NM_001071 (TYMS, Thymidylate synthetase), Genebank NM_002485 (NBN, nibrin), Gene Genebank NM_002592 (PCNA, proliferating cell nuclear antigen), Genebank NM_004219 (PTTG1, pituitary tumor-transforming 1), Genebank NM_005427 (TP73, Tumor protein p73), Gene Registration Number (Genebank) NM_005441 (CHAF1B, chromatin assembly factor 1, subunit B (p60)), gene registration number (Genebank) NM_005484 (PARP2, poly (ADP-ribose) polymerase family, Member 2), gene registration number (Genebank) NM_016218 ( POLK, polymerase (DNA directed) kappa), Genebank BC048985 (TAF15, TAF15 RNA polymerase II, TATA box binding protein (TBP) -associated factor, 68kDa), Genebank (Menebank) NM_001007101 (ZNF484, zinc finger protein 484), Genebank NM_002383 ( MAZ, MYC-associated zinc finger protein (purine-binding transcription factor), Genebank NM_003316 (TTC3, Tetratricopeptide repeat domain 3), Genebank NM_003410 (ZFX, zinc finger protein, X-linked ), Gene registration number (Genebank) NM_005060 (RORC, RAR-related orphan receptor C), gene registration number (Genebank) NM_006963 (ZNF22, zinc finger protein 22 (KOX 15)), gene registration number (Genebank) NM_014898 (ZFP30, zinc finger protein 30 homolog (mouse), Genebank NM_016019 (LUC7L2, LUC7-like 2 (S. cerevisiae)), Gene Registration Number (Genebank) NM_017661 (SUHW4, suppressor of hairy wing homolog 4 (Drosophila)), Gene Registration Number (Genebank) NM_021178 (CCNB1IP1, cyclin B1 interacting protein 1), Gene Registration Number (Genebank) NM_030899 ( ZNF323, zinc finger protein 323, Genebank NM_032268 (ZNRF1, zinc and ring finger 1), Genebank NM_033089 (ZCCHC3, zinc finger, cCHC domain containing 3), Genebank (Genebank) NM_152355 (ZNF441, zinc finger protein 441), Genebank (Genebank) NM_181756 (ZNF233, zinc finger protein 233), Genebank (Genebank) NM_182515 (ZNF714, zinc finger protein 714), Genebank AK131529 (Genebank) AATK, apoptosis-associated tyrosine kinase, Genebank NM_000289 (PFKM, phosphofructokinase, Muscle), Genebank NM_000553 (WRN, Werner syndrome), Genebank NM_001786 (CDC2, cell division cycle 2, g1 to S and G2 to M), Gene Registration Number (Genebank) NM_001813 (CENPE, centromere protein E, 312 kDa), Gene Registration Number (Genebank) NM_003579 (RAD54L, RAD54-like (S. cerevisiae)), Gene Registration Number (Genebank) NM_005964 (MYH10, Myosin, heavy chain 10, non-muscle), gene registration number (Genebank) NM_006306 (SMC1A, structural maintenance of chromosomes 1A), gene registration number (Genebank) NM_013257 (SGK3, serum / glucocorticoid regulated kinase family, Member 3), gene registration number ( Genebank) NM_014616 (ATP11B, aTPase, class VI, Type 11B), Gene Registration Number (Genebank) NM_015512 (DNAH1, dynein, axonemal, heavy chain 1), Gene Registration Number (Genebank) NM_016350 (NIN, ninein (GSK3B interacting protein) Genebank NM_018183 (SBNO1, strawberry notch homolog 1 (Drosophila)), Genebank NM_020159 (SMARCAD1, sWI / SNF-related, Matrix-associated actin-dependent regulator of chromatin, subfamily a, containing DEAD / H box 1), Gene Accession Number (Genebank) NM_024320 (ATAD4 , aTPase family, aAA domain containing 4), Genebank NM_024594 (PANK3, pantothenate kinase 3), Genebank NM_033151 (ABCC11, aTP-binding cassette, sub-family C (CFTR / MRP), Member 11), Gene Registration Number (Genebank) NM_182802 (MCM8, Minichromosome maintenance complex component 8), Gene Registration Number (Genebank) NM_207578 (PRKACB, protein kinase, cAMP-dependent, catalytic, Beta), Gene Registration Number (Genebank) NR_002451 (ABCA11, aTP-binding cassette, sub-family A (ABC1), Member 11 (pseudogene)), gene registration number (Genebank) AF042838 (MAP3K1, Mitogen-activated protein kinase kinase kinase 1), gene registration number (Genebank) AL117400 (PASK, pAS domain containing serine / threonine kinase), gene accession number (Genebank) NM_000221 (KHK, ketohexokinase (fructokinase)), gene accession number (Genebank) NM_001005735 (CHEK2, cHK2 checkpoint homolog (S. pombe), Genebank NM_001626 (AKT2, v-akt murine thymoma viral oncogene homolog 2), Genebank NM_001826 (CKS1B, cDC28 protein kinase regulatory subunit 1B), Genebank NM_002758 (MAP2K6, Mitogen-activated protein kinase kinase 6), gene registration number (Genebank) NM_005400 (PRKCE, protein kinase C, epsilon), gene registration number (Genebank) NM_006716 (DBF4, dBF4 homolog (S. cerevisiae)), gene registration Genebank NM_014215 (INSRR, insulin receptor-related receptor), Genebank NM_023110 (FGFR1, fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, pfeiffer syndrome), Genebank NM_032246 (RKHD3, Ring finger and KH domain containing 3), Gene Registration Number (Genebank) NM_052987 (CDK10, cyclin-dependent kinase (CDC2-like) 10), Gene Registration Number (Genebank) NM_001005526 (SF3B1, splicing factor 3b, subunit 1,155 kDa), Genebank NM_002138 (HNRPD, heterogeneous nuclear ribonucleoprotein D (AU-rich element RNA binding protein 1,37kDa), gene registration number (Genebank) NM_003400 (XPO1, exportin 1 (CRM1 homolog, Yeast)), gene registration number (Genebank) NM_004814 (WDR57, WD repeat domain 57 (U5 snRNP specific), Genebank NM_005033 (EXOSC9, exosome component 9), Genebank NM_006527 (SLBP, stem-loop (histone) binding protein), Genebank (Genebank) ) NM_006638 (RPP40, Ribonuclease P 40kDa subunit), gene registration number (Genebank) NM_006805 (HNRPA0, heterogeneous nuclear ribonucleoprotein A0), gene registration number (Genebank) NM_014953 (DIS3, dIS3 mitotic control homolog (S. cerevisiae)), gene registration number (Genebank) NM_032361 (THOC3, THO complex 3), gene registration number (Genebank) NM_152292 (RG9MTD2, RNA (guanine-9-) methyltransferase domain containing 2), gene registration number (Genebank) AF090937 ( SORBS2, sorbin and SH3 domain containing 2), Genebank NM_000583 (GC, group-specific component (vitamin D binding protein)), Genebank NM_001001290 (SLC2A9, solute carrier family 2 (facilitated glucose transporter) ), Member 9), Genebank NM_001045 (SLC6A4, solute carrier family 6 (neurotransmitter transporter, serotonin, Member 4), Genebank NM_003366 (UQCRC2, ubiquinol-cytochrome c reductase core protein II), Genebank NM_004896 (VPS26A, vacuolar protein sorting 26 homolog A (S.pombe)), Genebank number (Genebank) NM_006028 (HTR3B, 5-hydroxytryptamine (serotonin) receptor 3B), Genebank number NM_006359 (SLC9A6, solute carrier family 9 (so dium / hydrogen exchanger), Member 6), Genebank NM_006416 (SLC35A1, solute carrier family 35 (CMP-sialic acid transporter), Member A1), Gene accession number (Genebank) NM_006544 (EXOC5, exocyst complex component 5 ), Gene registration number (Genebank) NM_014229 (SLC6A11, solute carrier family 6 (neurotransmitter transporter, gABA), Member 11), gene registration number (Genebank) NM_016057 (COPZ1, coatomer protein complex, subunit zeta 1), gene registration number ( Genebank) NM_016320 (NUP98, nucleoporin 98kDa), Genebank Number (Genebank) NM_018155 (SLC25A36, solute carrier family 25, Member 36), Genebank Number (Genebank) NM_175623 (RAB3IP, RAB3A interacting protein (rabin3), Gene Registration Number (Genebank) AF256215 (ARNTL2, aryl hydrocarbon receptor nuclear translocator-like 2), gene accession number (Genebank) BC041387 (MCTP2, Multiple C2 domains, Transmembrane 2), gene accession number (Genebank) NM_000506 (F2, coagulation factor II (thrombin) )), Gene registration number (Genebank) NM_000820 (GAS6, growth arrest-specific 6), Gene Registration Number (Genebank) NM_002317 (LOX, Lysyl oxidase), Gene Registration Number (Genebank) NM_002834 (PTPN11, protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome) 1)), Gene Registration Number (Genebank) NM_003546 (HIST1H4L, histone cluster 1, h4l), Gene Registration Number (Genebank) NM_004311 (ARL3, aDP-ribosylation factor-like 3), Gene Registration Number (Genebank) NM_006203 (PDE4D, phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, drosophila), genebank NM_012096 (APPL1, adapter protein, phosphotyrosine interaction, pH domain and leucine zipper containing 1), genebank NM_012309 (SHANK2) , sH3 and multiple ankyrin repeat domains 2), Genebank NM_012425 (RSU1, Ras suppressor protein 1), Genebank NM_015547 (ACOT11, acyl-CoA thioesterase 11), Genebank NM_016022 (APH1A, anterior pharynx defec tive 1 homolog A (C. elegans)), Genebank NM_024718 (C9orf86, chromosome 9 open reading frame 86), Genebank NM_080651 (THRAP6, Thyroid hormone receptor associated protein 6), Genebank NM_181523 (PIK3R1, phosphoinositide-3-kinase, Regulatory subunit 1 (p85 alpha)), gene accession number (Genebank) NM_194455 (KRIT1, kRIT1, ankyrin repeat containing), gene accession number (Genebank) NM_002089 (CXCL2, chemokine (CXC motif) ligand 2) , Genebank (Genebank) NM_003810 (TNFSF10, Tumor necrosis factor (ligand) superfamily, Member 10), Genebank (Genebank) NM_003811 (TNFSF9, Tumor necrosis factor (ligand) superfamily, Member 9), Gene accession number (Genebank) ) NM_031479 (INHBE, inhibin, Beta E), Genebank (Genebank) NM_017915 (C12orf48, chromosome 12 open reading frame 48), Genebank (Genebank) BC021267 (KLHL14, kelch-like 14 (Drosophila))

In order to find out biomarkers for confirming exposure to indeno (1,2,3-c, d) pyrene, the inventors used indeno (1,2,3-c, d) pyrene as a human liver cancer cell line. Treatment with (HepG2) confirmed the cytotoxicity. As a result, it was confirmed that the indeno (1,2,3-c, d) pyrene is toxic to human liver cancer cell line (see Fig. 1), based on the experiment indeno (1,2,3-) c, d) The concentration of pyrene was determined. Then, indeno (1,2,3-c, d) pyrene is treated to human liver cancer cell line at the determined concentration, mRNA is isolated from the cell line treated with the substance, and labeled with fluorescent material (Cy5) while synthesizing cDNA. In the case of the drug-free control group, it was labeled with Cy3. The fluorescently labeled cDNA was hybridized with a human whole genome microarray (Agilent, USA), a 44 k oligomicroarray chip, and analyzed for differences in gene expression patterns by scanning fluorescent images (see FIG. 2). In the analysis, when the Cy5 / Cy3 ratio was 1.5 times or more, it was classified as an expression increased gene. As a result, it was confirmed that the gene with increased expression was 1.04% (458 of 44,000 genes) and the gene with reduced expression was 1.11% (490 of 44,000 genes). In this case, when the genes that are overexpressed or underexpressed by the indeno (1,2,3-c, d) pyrene are classified by the function classified by cell death, zinc-finger ), Enzyme regulator activity, cell proliferation, regulation of Transcription, oxidoreductase activity, ligase activity, immune response, Signal transducer activity, cytoskeleton, macromolecular catabolism, DNA binding, cell cycle, DNA repair, zinc-finger finger, ATP binding, kinase activity, RNA processing, transport, signal transduction, cytokine-cytokine receptor interaction ) And related genes (see Table 2 and Table 3). The genes are not reported to be associated with toxicity in human liver cancer cells when treated with indeno (1,2,3-c, d) pyrene used in the present invention.

In addition, the present invention is a DNA microorganism for confirming the exposure to indeno (1,2,3-c, d) pyrene in which the oligonucleotide containing the whole or part of the biomarker gene sequence or its complementary strand molecule is integrated Provides an array chip.

The oligonucleotide or complementary strand molecule thereof comprises 18 to 30 nucleic acids of the biomarker gene, preferably 20 to 25 nucleic acids.

The DNA microarray chip for indeno (1,2,3-c, d) pyrene search of the present invention can be produced by a method known to those skilled in the art. The method of manufacturing the microarray chip is as follows. In order to immobilize the searched biomarker as a probe DNA molecule on a substrate of a DNA chip, a micropipetting method or a pin-shaped spotter using a piezoelectric method is used. It is preferable to use the method, but the present invention is not limited thereto. In a preferred embodiment of the present invention, a microarray, which is a pin-shaped spotter, is used. The substrate of the DNA microarray chip is preferably coated with one active group selected from the group consisting of amino-silane, poly-L-lysine, and aldehyde. It is not limited. In addition, the substrate may be selected from the group consisting of slide glass, plastic, metal, silicon, nylon membrane, and nitrocellulose membrane, but is not limited thereto, and in the preferred embodiment of the present invention, amino-silane may be used. Coated slide glass was used.

In addition, the present invention provides a method for confirming exposure to indeno (1,2,3-c, d) pyrene using the biomarker.

The present invention provides a method for confirming exposure to indeno (1,2,3-c, d) pyrene comprising the following steps:

1) separating RNA from cells obtained in the subject and untreated human cells as controls;

2) synthesizing RNA of the experimental group and the control group of step 1) with cDNA and labeling the fluorescent substance of each of the experimental group and the control group;

3) hybridizing cDNA labeled with different fluorescent materials of step 2) with the DNA microarray chip of the present invention;

4) analyzing the reacted DNA microarray chip of step 3); And

5) comparing the expression level of the biomarker of the present invention in the analyzed data of step 4) with the control to determine whether indeno (1,2,3-c, d) pyrene exposure.

In the method of confirming the exposure, the cell of step 1) is preferably derived from human tissue or blood, but is not limited thereto.

In the method for confirming the exposure, the fluorescent material of step 2) is Cy3, Cy5, poly L-lysine-fluorescein isothiocyanate (FITC), RITC (rhodamine-B-isothiocyanate) and rhodamine (rhodamine) It is preferable to be selected, but not limited thereto, and any fluorescent material known to those skilled in the art may be used.

In the method for confirming the exposure, the DNA microarray chip of step 4) is preferably using Whole Human Genome Oligo Microarray (Agilent, USA) and the like, but is not limited thereto. As long as it is a microarray chip loaded with an over- or low-expression gene (see Tables 2 and 3), it is most preferable to use a DNA microarray chip produced by the present inventors. In addition, the analysis method of step 5) preferably uses GenePix 4.1 software (Axon Instruments, USA), but is not limited thereto, and analysis software known to those skilled in the art may be used.

In addition, the present invention provides a kit for confirming the exposure to indeno (1,2,3-c, d) pyrene.

In the kit, it provides a kit for confirming the exposure to indeno (1,2,3-c, d) pyrene comprising the DNA microarray chip prepared in the present invention.

In addition, in the kit, it is confirmed whether the exposure to indeno (1,2,3-c, d) pyrene containing a primer pair of 10 ~ 100 bp length that can specifically amplify the biomarker of the present invention Provide a kit for

In addition to the kit may include a fluorescent material, the fluorescent material from the group consisting of a strepavidin-alkaline phosphatase conjugate (chemreplurensce) and chemiluminescent (chemiluminescent) Preferably, but not limited thereto, Cy3 and Cy5 were used in the preferred embodiment of the present invention.

The kit may additionally include a reaction reagent, which is a buffer used for hybridization, reverse transcriptase for synthesizing cDNA from RNA, cNTPs and rNTP (premixed or separated feed), chemical inducer of fluorescent dyes It may be composed of a labeling reagent, such as a washing buffer, but is not limited thereto, and may include all reaction reagents required for hybridization of DNA microarray chips known to those skilled in the art.

Hereinafter, the present invention will be described in detail by way of examples.

However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.

Example 1 Cell Culture and Chemical Treatment

<1-1> Cell Culture

HepG2 cells (Korea Cell Line Bank), which is a human liver cancer cell line, were cultured in DMEM medium (Gibro-BRL, USA) to which 10% FBS was added until 80% growth in 100 mm dish. The present inventors have selected indeno (1,2,3-c, d) pyrene, a substance having carcinogenicity, as one of the polycyclic aromatic hydrocarbons through existing studies and reports, and dissolved in DMSO. Vehicle concentration was less than 0.1% in all experiments.

<1-2> MTT assay and chemical treatment

MTT experiment using HepG2 cell line was performed by the method of Mossman et al. ( J. Immunol. Methods , 65, 55-63, 1983). Cells were treated with indeno (1,2,3-c, d) pyrene dissolved in DMSO in DMEM medium (Gibro-BRL, USA) at 4 × 10 ⁵ / well cell number in 24-well plates for 48 hours. After 5 mg / ㎖ of MTT (3-4, 5-dimethylthiazol-2, 5-diphenyltetra zolium bromide) was mixed and added to the tube and incubated for 3 hours at 37 ℃. Thereafter, the medium was removed and the formed formazan crystal was dissolved in 500 µl of DMSO. Transfer to a 96-well plate was aliquoted and the OD value was measured at absorbance 540 nm.

The cytotoxicity of indeno (1,2,3-c, d) pyrene in HepG2 cell line showed that 20% viable concentration (IC ₂₀ ) was 227.76 uM (see FIG. 1), determined by these concentrations. Microarray experiments were performed.

Example 2 Microarray Experiment

<2-1> Isolation of Target RNA and Fluorescent Labeling

After dispensing HepG2 cells in a 100 mm dish at a concentration of 6 × 10 ⁶ cells / ml, the concentration of indeno (1,2,3-c, d) pyrene determined in Example 1-2 was treated for 48 hours. . Thereafter, the whole cells were separated from the treated cells using a trizol reagent (Invitrogen life technologies, USA) according to the manufacturer's method, and purified using the RNeasy mini kit (Qiagen, USA). Genomic DNA was removed using RNase-free DNase set (Qiagen, USA) during RNA purification. The amount of each total RNA sample was measured by spectrophotometer, the concentration was confirmed by Experion (Automated Electrophoresis station, Bio-Rad).

<2-2> Labeled cDNA Preparation

CDNA was prepared using the total RNA of the indeno (1,2,3-c, d) pyrene treatment group obtained in Example 2-1 for oligo microarray analysis. The total RNA obtained above was mixed with 30 μg of oligo (dT) primer and 2 μg (1 μg / μl), reacted at 65 ° C. for 10 minutes, and then annealed in ice. Reagents were mixed as shown in Table 1 for Reverse Transcript reaction of the annealed RNA.

Configuration Volume (μl) 5X first strand buffer 6 dNTPs 0.6 0.1 M DDT 3 SuperScript II enzyme 3 Cy-3 or Cy-5 dUTP 2

Total RNA isolated from control HepG2 cell line was labeled with Cy3-dUTP (green), and RNA isolated from HepG2 cell line treated with indeno (1,2,3-c, d) pyrene was Cy5-dUTP (red). ). At this time, the two samples were mixed and purified using a Microcon YM-30 column (Millipore, USA).

<2-3> hybridization reaction

Hybridization and washing procedures were carried out according to the instructions of Genome Co., Ltd .. Hybridization was performed in a 62 ° C. oven for 12 hours. 44 k Whole Human Genome Oligo Microarray (Agilent, USA) was used as the DNA microarray chip. After washing (washing in 2 × SSC / 0.1% SDS for 2 minutes, washing in 1 × SSC for 3 minutes, 0.2 × SSC for 2 minutes), the slides were dried by centrifugation at 800 rpm for 3 minutes.

<2-4> Fluorescence Image Acquisition

Hybridization images on the slides were scanned with the Genepix 4000B (Axon Instruments, USA). Chips washed with unbound genes were obtained with a fluorescence image using a laser fluorescence scanner. In this case, the green fluorescence image in the control group, the red fluorescence image represents the activity level of the gene specifically expressed only in the experimental group, and the yellow fluorescence image is the complementary color of green and red, which means that there is no significant difference between the two groups. Scanned images were analyzed with GenePix 4.1 software (Axon Instruments, USA) to obtain gene expression rates. Marker genes for indeno (1,2,3-c, d) pyrene were selected from the data thus obtained (see FIG. 2).

As a result, among the approximately 44,000 genes present on the oligo chip, the ratio of Cy5 / Cy3 was increased 1.5 times or more by indeno (1,2,3-c, d) pyrene. Was 1.04% (458 out of 44,000 genes) and 1.11% (490 out of 44,000 genes) reduced expression.

In this case, the genes overexpressed or underexpressed by indeno (1,2,3-c, d) pyrene by 1.5 times or more were classified according to their function, resulting in cell death and zinc-finger. , Enzyme regulator activity, cell proliferation, regulation of Transcription, oxidoreductase activity, ligase activity, immune response, signaling Signal transducer activity, cytoskeleton, macromolecular catabolism, DNA binding, cell cycle, DNA repair, zinc-finger ), ATP binding, kinase activity, RNA processing, transport, signal transduction, cytokine-cytokine receptor interaction ) (Tables 2 and 3). The genes have not been reported to be associated with toxicity in human liver cancer cells when treated with indeno (1,2,3-c, d) pyrene used in the present invention.

Indeno (1,2,3-c, d) pyrene  Genes with increased expression Registration Number Gene abbreviation Gene name Ratio of medians (a) cell death NM_000606 C8G complement component 8, gamma polypeptide 2.18403 NM_001429 EP300 E1A binding protein p300 1.61558 NM_003804 RIPK1 receptor (TNFRSF) -interacting serine-threonine kinase 1 1.67173 NM_003806 HRK harakiri, BCL2 interacting protein (contains only BH3 domain) 1.74245 NM_003901 SGPL1 sphingosine-1-phosphate lyase 1 1.5507 NM_004049 BCL2A1 BCL2-related protein A1 1.51008 NM_006437 PARP4 poly (ADP-ribose) polymerase family, member 4 1.64036 NM_020371 Aven apoptosis, caspase activation inhibitor 1.54841 NM_022094 CIDEC cell death-inducing DFFA-like effector c 1.91773 NM_022151 MOAP1 modulator of apoptosis 1 1.51666 NM_133369 UNC5A unc-5 homolog A (C.elegans) 1.50376 NM_138578 BCL2L1 BCL2-like 1 1.5978 (b) zinc - finger AB040944 ZSWIM5 zinc finger, SWIM-type containing 5 1.5955 AF144233 ZMYND8 zinc finger, MYND-type containing 8 1.57871 NM_000176 NR3C1 nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) 1.7325 NM_002180 IGHMBP2 immunoglobulin mu binding protein 2 1.7056 NM_006254 PRKCD protein kinase C, delta 1.68586 NM_016213 TRIP4 thyroid hormone receptor interactor 4 1.58815 NM_019062 RNF186 ring finger protein 186 1.63565 NM_022482 GZF1 GDNF-inducible zinc finger protein 1 1.62417 NM_033092 TRIM5 tripartite motif-containing 5 1.5348 NM_138287 DTX3L deltex 3-like (Drosophila) 1.66007 NM_145288 ZNF342 zinc finger protein 342 1.56397 NM_173548 ZNF584 zinc finger protein 584 1.52669 NM_930521 ZNF506 zinc finger protein 506 1.65819 (c) enzyme regulator activity BX648244 SPATA13 spermatogenesis associated 13 1.71796 CR599277 SERPINB2 serpin peptidase inhibitor, clade B (ovalbumin), member 2 17.3457 NM_000308 CTSA cathepsin A 1.67889 NM_001002857 ANXA2 annexin A2 1.78407 NM_001320 CSNK2B casein kinase 2, beta polypeptide 1.54195

NM_001750 CAST calpastatin 1.54361 NM_004152 OAZ1 ornithine decarboxylase antizyme 1 1.61299 NM_006869 CENTA1 centaurin, alpha 1 1.50004 NM_014889 PITRM1 pitrilysin metallopeptidase 1 1.54496 NM_014916 LMTK2 lemur tyrosine kinase 2 1.61312 NM_015941 ATP6V1H ATPase, H + transporting, lysosomal 50 / 57kDa, V1 subunit H 1.5796 NM_018482 DDEF1 development and differentiation enhancing factor 1 1.5754 NM_018993 RIN2 Ras and Rab interactor 2 1.81825 NM_032258 TBC1D3 TBC1 domain family, member 3 1.69709 NM_058197 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 2.11228 NM_198681 PLEKHG5 pleckstrin homology domain containing, family G (with RhoGef domain) member 5 1.61189 (d) cell proliferation BC002828 AGGF1 angiogenic factor with G patch and FHA domains 1 1.52068 NM_000875 IGF1R insulin-like growth factor 1 receptor 1.72633 NM_001562 IL18 interleukin 18 (interferon-gamma-inducing factor) 1.81668 NM_002831 PTPN6 protein tyrosine phosphatase, non-receptor type 6 1.55193 NM_003999 OSMR oncostatin M receptor 1.55263 NM_004624 VIPR1 vasoactive intestinal peptide receptor 1 7.30891 NM_005557 KRT16 keratin 16 (focal non-epidermolytic palmoplantar keratoderma) 1.51258 NM_005755 EBI3 Epstein-Barr virus induced gene 3 1.62235 NM_007063 TBC1D8 TBC1 domain family, member 8 (with GRAM domain) 1.72075 NM_016558 SCAND1 SCAN domain containing 1 1.94141 NM_032965 CCL15 chemokine (C-C motif) ligand 15 1.58984 (e) regulation of transcription AF343007 FOXC1 forkhead box C1 1.60522 AK074757 ZNF253 zinc finger protein 253 1.66171 BC063666 CREB3L2 cAMP responsive element binding protein 3-like 2 1.76915 NM_001010926 HES5 hairy and enhancer of split 5 (Drosophila) 1.68322 NM_002167 ID3 inhibitor of DNA binding 3, dominant negative helix-loop-helix protein 1.6084 NM_002501 NFIX nuclear factor I / X (CCAAT-binding transcription factor) 2.04912 NM_003107 SOX4 SRY (sex determining region Y) -box 4 1.50312 NM_003475 RASSF7 Ras association (RalGDS / AF-6) domain family 7 1.80498 NM_005315 GSCL goosecoid-like 1.64178 NM_005848 DENND4A DENN / MADD domain containing 4A 1.5071 NM_005902 SMAD3 SMAD family member 3 1.50782 NM_006663 PPP1R13L protein phosphatase 1, regulatory (inhibitor) subunit 13 like 1.50116 NM_007005 TLE4 transducin-like enhancer of split 4 (E (sp1)) holog, Drosophila 1.56417 NM_012240 SIRT4 sirtuin (silent mating type information regulation 2 homolog) 4 (S.cerevisiae) 1.5733 NM_014368 LHX6 LIM homeobox 6 1.50959 NM_015481 ZNF385 zinc finger protein 385 1.50048 NM_016170 TLX2 T-cell leukemia homeobox 2 1.69247 NM_021961 TEAD1 TEA domain family member 1 (SV40 transcriptional enhancer factor) 1.51783 NM_130439 MXI1 MAX interator 1 1.50503 NM_152287 ZNF276 zinc finger protein 276 1.64014 NM_207305 FOXD4 forkhead box D4 1.52118 (f) oxidoreductase activity BC035714 CYP19A1 cytochrome P450, family 19, subfamily A, polypeptide 1 1.5613 NM_000603 NOS3 nitric oxide synthase 3 (endothelial cell) 1.86938 NM_000761 CYP1A2 cytochrome P450, family 1, subfamily A, polypeptide 2 1.50002 NM_001013660 FRRS1 ferric-chelate reductase 1 1.53689 NM_004542 NDUFA3 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 3, 9 kDa) 1.53198 NM_005390 PDHA2 pyruvate dehydrogenase (lipoamide) alpha 2 1.57173 NM_005625 SDCBP syndecan binding protein (syntenin) 1.55727 NM_006157 NELL1 NEL-like 1 (chicken) 1.57435 NM_017460 CYP3A4 cytochrome P450, family 3, subfamily A, polypeptide 4 1.97066 NM_019885 CYP26B1 cytochrome P450, family 26, subfamily B, polypeptide 1 1.50257 NM_022051 EGLN1 eg 1 nine homolog 1 (C. elegans) 1.5322 NM_032783 CBR4 carbonyl reductase 4 1.9226 NM_145690 YWHAZ tyrosine 3-monooxygenase / tryptophan 5-monooxygenase activation protein, zeta polypeptide 1.54562 NM_207352 CYP4V2 cytochrome P450, family 4, subfamily V, polypeptide 2 1.54084 (g) ligase activity NM_002047 GARS glycyl-tRNA synthetase 1.59482 NM_003344 UBE2H ubiquitin-conjugating enzyme E2H (UBC8 homolog, yeast) 1.51521 NM_003729 RTCD1 RNA terminal phosphate cyclase domain 1 1.65727 NM_005358 LMO7 LIM domain 7 1.50667 NM_006292 TSG101 tumor susceptibility gene 101 1.50977 NM_032673 PCGF1 polycomb group ring finger 1 1.65539 NM_178532 RNF180 ring finger protein 180 1.51374 (h) immune response AF031469 MR1 major histocompatibility complex, class I-related 1.78219 BC029781 C2 complement component 2 1.51703 NM_000623 BDKRB2 bradykinin receptor B2 1.50159 NM_001065 TNFRSF1A tumor necrosis factor receptor superfamily, member 1A 1.52636 NM_001838 CCR7 chemokine (C-C motif) receptor 7 2.29799 NM_002119 HLA-DOA major histocompatibility complex, class Ⅱ, DO alpha 1.69429 NM_002184 IL6ST interleukin 6 signal transducer (gp130, oncostatin M receptor) 1.53803 NM_002259 KLRC1 killer cell lectin-like receptor subfamily C, member 1 3.84648 NM_005018 PDCD1 programmed cell death 1 1.70018 NM_006866 LILRA2 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 2 1.54713 NM_014314 DDX58 DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 1.58106 NM_016232 IL1RL1 interleukin 1 receptor-like 1 1.53592 NM_018284 GBP3 guanylate binding protein 3 1.80257 NM_021034 IFITM3 interferon induced transmembrane protein 3 (1-8U) 1.63736 NM_031409 CCR6 chemokine (C-C motif) receptor 6 1.57473 NM_203330 CD59 CD59 molecule, complement regulatory protein 1.58739 (i) signal transducer activity AF078165 AXIN2 axin 2 (conductin, axil) 1.62782 NM_000419 ITGA2B integrin, alpha 2b (platelet glycoprotein IIb of IIb / IIIa complex, antigen CD41) 1.5253 NM_000758 CSF2 colony stimulating factor 2 (granulocyte-macrophage) 2.02132 NM_001124 ADM adrenomedullin 1.62775 NM_001381 DOK1 docking protein 1, 62kDa (downstream of tyrosine kinase 1) 1.58735 NM_002010 FGF9 fibroblast growth factor 9 (glia-activating factor) 1.58675 NM_002088 GRIK5 glutamate receptor, ionotropic, kainate 5 1.68826 NM_002222 ITPR1 inositol 1,4,5-triphosphate receptor, type 1 1.76371 NM_002224 ITPR3 inositol 1,4,5-triphosphate receptor, type 3 1.54287 NM_002350 LYN v-yes-1 Yamaguchi sarcoma viral related oncogene homolog 1.60412 NM_002561 P2RX5 purinergic receptor P2X, ligand-gated ion channel, 5 1.53845 NM_003979 GPRC5A G protein-coupled receptor, family C, group 5, member A 1.70809 NM_004672 MAP3K6 mitogen-activated protein kinase kinase kinase 6 1.61302 NM_004843 IL27RA interleukin 27 receptor, alpha 1.56967 NM_005297 MCHR1 melanin-concentrating member receptor 1 1.59155 NM_022772 EPS8L2 EPS8-like 2 1.67847 NM_030571 NDFIP1 Nedd4 family interacting protein 1 1.51376 NM_032174 TOMM40L translocase of outer mitochondrial membrane 40 homolog (yeast) -like 1.51637 NM_058172 ANTXR2 anthrax toxin receptor 2 1.59953 NM_153002 GPR156 G protein-coupled receptor 156 1.62401 NM_181501 ITGA1 integrin, alpha 1 1.61321 NM_182665 RASSF5 Ras association (RalGDS / AF-6) domain family 5 1.80457 (j) cytoskeleton AB210045 KIF5A kinesin family member 5A 1.61665 BC010091 BICD1 bicaudal D homolog 1 (Drosophila) 3.1806 BC027875 MY015B myosin XVB pseudogene 1.75927 NM_002213 ITGB5 interin, beta 5 1.58259 NM_004735 LRRFIP1 leucine rich repeat (in FLII) interacting protein 1 1.8358 NM_005231 CTTN cortactin 1.56801 NM_005507 CFL1 cofilin 1 (non-muscle) 1.58366 NM_006091 CORO2B coronin, actin binding protein, 2B 1.5711 NM_006380 APPBP2 amyloid beta precursor protein (cytoplasmic tail) binding protein 2 1.56079 NM_012144 DNAI1 dynein, axonemal, intermediate chain 1 1.53219 NM_015990 KLHL5 kelch-like 5 (Drosophila) 1.98698 NM_018222 PARVA parvin, alpha 1.76848 NM_021109 TMSB4X thymosin, beta 4, X-linked 1.50433 NM_022765 MICAL1 microtubule associated monoxygenase, calponin and LIM domain containing 1 1.97204 NM_031308 EPPK1 epiplakin 1 1.51565 NM_033375 MYO1C myosin ic 1.61161 NM_080881 DBN1 drebrin 1 1.604 NM_152237 GAS2L1 growth arrest-specific 2 like 1 1.50151 NM_213636 PDLIM7 PDZ and LIM domain 7 (enigma) 1.5516 (k) macromolecule catabolism NM_000021 PSEN1 presenilin 1 (Alzheimer disease 3) 1.54013 NM_002034 FUT5 fucosyltransferase 5 (alpha (1,3) fucosyltransferase 1.50549 NM_002046 GAPDH glyceraldehyde-3-phosphate dehydrogenase 1.58786 NM_002392 MDM2 Mdm2, transformed 3T3 cell double minute 2, p53 binding protein (mouse) 1.61567 NM_003333 UBA52 ubiquitin A-52 residue ribosomal protein fusion product 1 1.55431 NM_004505 USP6 ubiquitin specific peptidase 6 (Tre-2 oncogene) 1.54258 NM_005805 PSMD14 proteasome (prosome, macropain) 26S subunit, non-ATPase, 14 1.72067 NM_013396 USP25 ubiquitin specific peptidase 25 1.61155 NM_017584 MIOX myo-inositol oxygenase 1.58204 NM_021009 UBC ubiquitin C 1.61525 NM_032582 USP32 ubiquitin specific peptidase 32 1.64482 NM_033500 HK1 hexokinase 1 7.03743 (l) DNA binding NM_001310 CREBL2 cAMP responsive element binding protein-like 2 1.53755 NM_002166 ID2 inhibitor of DNA binding 2, dominant negative helix-loop-helix protein 1.59934 NM_002622 PFDN1 prefoldin subunit 1 1.5553 NM_003113 SP100 SP100 nuclear antigen 1.55159 NM_005419 STAT2 signal transducer and activator of transcription 2, 113 kDa 1.51966 NM_005526 HSF1 heat shock transcription factor 1 1.56564 NM_005920 MEF2D myocyte enhancer factor 2D 1.51367 NM_014212 HOXC11 homeobox C11 1.80598 NM_014423 AFF4 AF4 / FMR2 family, member 4 1.73644 NM_015106 RAD54L2 RAD54-like 2 (S, cerevisiae) 1.51306 NM_017422 CALML5 calmodulin-like 5 1.62965 NM_032292 GON4L gon-4-like (C. elegans) 1.52057 NM_134424 RAD52 RAD52 homolog (S. cerevisiae) 1.57783 NM_144631 ZNF513 zinc finger protein 513 1.513

Indeno (1,2,3-c, d) pyrene  Genes whose expression is reduced Registration Number Gene abbreviation Gene name Ratio of medians (a) cell cycle NM_001012334 MDK midkine (neurite growth-promoting factor 2) 0.61753 NM_001761 CCNF cyclin F 0.6639 NM_001789 CDC25A cell division cycle 25 homolog A (S. pombe) 0.50049 NM_002823 PTMA prothymosin, alpha (gene sequence 28) 0.65482 NM_007295 BRCA1 breast cancer 1, early onset 0.48365 NM_014221 MTCP1 mature T-cell proliferation 1 0.66469 NM_014708 KNTC1 kinetochore associated 1 0.38355 NM_015097 CLASP2 cytoplasmic linker associated protein 2 0.64862 NM_018151 RIF1 RAP1 interacting factor homolog (yeast) 0.39304 (b) transcription regulation AL117645 MED28 mediator of RNA polymerase II transcription, subunit 28 homolog (S.cerevisiae) 0.6589 BC042297 UBTF upstream binding transcription factor, RNA polymerase I 0.64464 NM_000449 RFX5 regulatory factor X, 5 (influences HLA class II expression) 0.66429 NM_001032372 ZNF226 zinc finger protein 226 0.66451 NM_003216 TEF thyrotrophic embryonic factor 0.58074 NM_003411 ZFY zinc finger protein, Y-linked 0.63756 NM_003865 HESX1 HESX homeobox 1 0.56475 NM_003920 TIMELESS timeless homolog (Drosophila) 0.56652 NM_005254 GABPB2 GA binding protein transcription factor, beta subunit 2 0.62568 NM_006089 SCML2 sex comb on midleg-like 2 (Drosophila) 0.58296 NM_006454 MXD4 MAX dimerization protein 4 0.66233 NM_006530 YEATS4 YEATS domain containing 4 0.48081 NM_013249 ZNF214 zinc finger protein 214 0.61921 NM_014288 ITGB3BP integrin beta 3 binding protein (beta3-endonexin) 0.64753 NM_016578 RSF1 remodeling and spacing factor 1 0.61403 NM_018645 HES6 hairy and enhancer of split 6 (Drosophila) 0.66631 NM_020062 SLC2A4RG SLC2A4 regulator 0.59174 NM_021148 ZNF273 zinc finger protein 273 0.50358 NM_021269 ZNF708 zinc finger protein 708 0.61461 NM_025027 ZNF606 zinc finger protein 606 0.59511 NM_144566 ZNF700 zinc finger protein 700 0.66494 NM_175910 ZNF493 zinc finger protein 493 0.55479 NM_198968 DZIP1 DAZ interacting protein 1 0.63437 Y09321 TAF4B TAF4b RNA polymerase II, TATA box binding protein (TBP) -associated factor, 105 kDa 0.59177 (c) DNA repair NM_000251 MSH2 mutS homolog 2, colon cancer, nonpolypoosis type 1 (E. coli) 0.26646 NM_001039651 C6orf26 chromosome 6 open reading frame 26 0.38961 NM_001071 TYMS thymidylate synthetase 0.59807 NM_002485 NBN nibrin 0.47977 NM_002592 PCNA proliferating cell nuclear antigen 0.55179 NM_004219 PTTG1 pituitary tumor-transforming 1 0.58203 NM_005427 TP73 tumor protein p73 0.49154 NM_005441 CHAF1B chromatin assembly factor 1, subunit B (p60) 0.43369 NM_005484 PARP2 poly (ADP-ribose) polymerase family, member 2 0.66096 NM_016218 POLK polymerase (DNA directed) kappa 0.65076 (d) zinc - finger BC048985 TAF15 TAF15 RNA polymerase II, TATA box binding protein (TBP) -associated factor, 68 kDa 0.66215 NM_001007101 ZNF484 zinc finger protein 484 0.65979 NM_002383 MAZ MYC-associated zinc finger protein (purine-binding transcription factor) 0.58172 NM_003316 TTC3 tetratricopeptide repeat domain 3 0.37665 NM_003410 ZFX zinc finger protein, X-linked 0.66213 NM_005060 RORC RAR-related orphan receptor C 0.25812 NM_006963 ZNF22 zinc finger protein 22 (KOX 15) 0.54693 NM_014898 ZFP30 zinc finger protein 30 homolog (mouse) 0.64642 NM_016019 LUC7L2 LUC7-like 2 (S. cerevisiae) 0.64034 NM_017661 SUHW4 suppressor of hairy wing homolog 4 (Drosophila) 0.33149 NM_021178 CCNB1IP1 cyclin B1 interacting protein 1 0.64537 NM_030899 ZNF323 zinc finger protein 323 0.64739 NM_032268 ZNRF1 zinc and ring finger 1 0.63976 NM_033089 ZCCHC3 zinc finger, CCHC domain containing 3 0.6138 NM_152355 ZNF441 zinc finger protein 441 0.5304 NM_181756 ZNF233 zinc finger protein 233 0.59234 NM_182515 ZNF714 zinc finger protein 714 0.56168 (e) ATP binding AK131529 AATK apoptosis-associated tyrosinase kinase 0.58857 NM_000289 PFKM phosphofructokinase, muscle 0.63614 NM_000553 WRN Werner syndrome 0.65276 NM_001786 CDC2 cell division cycle 2, G1 to S and G2 to M 0.20217 NM_001813 CENPE centromere protein E, 312kDa 0.17706 NM_003579 RAD54L RAD54-like (S. cerevisiae) 0.60478 NM_005964 MYH10 myosin, heavy chain 10, non-muscle 0.51074 NM_006306 SMC1A structural maintenance of chromosomes 1A 0.62185 NM_013257 SGK3 serum / glucocorticoid regulated kinase family, member 3 0.63977 NM_014616 ATP11B ATPase, Class VI, type 11B 0.64043 NM_015512 DNAH1 dynein, axonemal, heavy chain 1 0.66283 NM_016350 NIN ninein (GSK3B interacting protein) 0.62734 NM_018183 SBNO1 strawberry notch homolog 1 (Drosophila) 0.62323 NM_020159 SMARCAD1 SWI / SNF-related, matrix-associated actin-dependent regulator of chromatin, subfamily a, containing DEAD / H box 1 0.62014 NM_024320 ATAD4 ATPase family, AAA domain containing 4 0.55154 NM_024594 PANK3 pantothenate kinase 3 0.58411 NM_033151 ABCC11 ATP-binding cassette, sub-family C (CFTR / MRP), member 11 0.65822 NM_182802 MCM8 minichromosome maintenance complex component 8 0.56324 NM_207578 PRKACB protein kinase, cAMP-dependent, catalytic, beta 0.65395 NM_002451 ABCA11 ATP-binding cassette, sub-family A (ABC1), meber 11 (pseudogene) 0.61392 (f) kinase activity AF042838 MAP3K1 mitogen-activated protein kinase kinase kinase 1 0.64095 AL117400 PASK PAS domain containing serine / threonine kinase 0.52317 NM_000221 KHK ketohexokinase (fructokinase) 0.61125 NM_001005735 CHEK2 CHK2 checkpoint homolog (S. pombe) 0.61405 NM_001626 AKT2 v-akt murine thymoma viral oncogene homolog 2 0.60083 NM_001826 CKS1B CDC28 protein kinase regulatory subunit 1B 0.54225 NM_002758 MAP2K6 mitogen-activated protein kinase kinase 6 0.09413 NM_005400 PRKCE protein kinase C, epsilon 0.31369 NM_006716 DBF4 DBF4 homolog (S. cerevisiae) 0.37212 NM_014215 INSRR insulin receptor-related receptor 0.2478 NM_023110 FGFR1 fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, Pfeiffer syndrome) 0.62415 NM_032246 RKHD3 ring finger and KH domain containing 3 0.60746 NM_052987 CDK10 cyclin-dependent kinase (CDC2-like) 10 0.58692 (g) RNA processing NM_001005526 SF3B1 splicing factor 3b, subunit 1, 155 kDa 0.62243 NM_002138 HNRPD heterogeneous nuclear ribonucleoprotein D (AU-rich element RNA binding protein 1, 37kDa) 0.65912 NM_003400 XPO1 exportin 1 (CRM1 homolog, yeast) 0.62175 NM_004814 WDR57 WD repeat domain 57 (US5 snRNP specific) 0.65541 NM_005033 EXOSC9 exosome component 9 0.61822 NM_006527 SLBP stem-loop (histone) binding protein 0.6338 NM_006638 RPP40 ribonuclease P 40 kDa subunit 0.64272 NM_006805 HNRPAO heterogeneous nuclear ribonucleoprotein AO 0.64958 NM_014953 DIS3 DIS3 mitotic control homolog (S. cerevisiae) 0.63467 NM_018048 mago-nashi homolog 2 0.64061 NM_032361 THOC3 THO complex 3 0.63374 NM_152292 RG9MTD2 RNA (guanine-9-) methyltransferase domain containing 2 0.66367 (h) transport AF090937 SORBS2 sorbin and SH3 domain containing 2 0.61001 NM_000583 GC group-specific component (vitamin D binding protein) 0.50431 NM_001001290 SLC2A9 solute carrier family 2 (facilitated glucose transporter), member 9 0.53944 NM_001045 SLC6A4 solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 0.62764 NM_003366 UQCRC2 ubiquinol-cytochrome c reductase core protein II 0.65733 NM_004896 VPS26A vacuolar protein sorting 26 homolog A (S.pombe) 0.65835 NM_006028 HTR3B 5-hydroxytryptamine (serotonin) receptor 3B 0.64176 NM_006359 SLC9A6 solute carrier family 9 (sodium / hydrogen exchanger), member 6 0.65332 NM_006416 SLC35A1 solute carrier family 35 (CMP-sialic acid transporter), member A1 0.65201 NM_006544 EXOC5 exocyst complex component 5 0.64406 NM_014229 SLC6A11 solute carrier family 6 (neurotransmitter transporter, GABA), member 11 0.62452 NM_016057 COPZ1 coatomer protein complex, subunit zeta 1 0.63772 NM_016320 NUP98 nucleoporin 98kDa 0.64272 NM_018155 SLC25A36 solute carrier family 25, member 36 0.63449 NM_175623 RAB3IP RAB3A interacting protein (rabin 3) 0.56044 (i) signal trnasduction AF256215 ARNTL2 aryl hydrocarbon receptor nuclear translocator-like 2 0.59073 BF041387 MCTP2 multiple C2 domains, trnasmembrane 2 0.36012 NM_000506 F2 coagulation fator II (thrombin) 0.65043 NM_000820 GAS6 growth arrest-specific 6 0.62074 NM_002317 LOX lysyl oxidase 0.45954 NM_002834 PTPN11 prtein tyrosine phosphate, non-receptor type II (Noonan syndrome 1) 0.66333 NM_003546 HIST1H4L histone cluster 1, H41 0.5005 NM_004311 ARL3 ADP-ribosylation factor-like 3 0.65318 NM_006203 PDE4D phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila) 0.6324 NM_012096 APPL1 adapter protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1 0.62949 NM_012309 SHANK2 SH3 and multiple ankyrin repeat domains 2 0.20932 NM_012425 RSU1 Ras suppressor protein 1 0.64934 NM_015547 ACOT11 acyl-CoA thioesterase 11 0.6145 NM_016022 APH1A anterior pharynx defective 1 homolog A (C. elegans) 0.64747 NM_024718 C9orf86 chromosome 9 open reading frame 86 0.66356 NM_080651 THRAP6 thyroid hormone receptor associated protein 6 0.61525 NM_181523 PIK3RI phosphoinositide-3-kinase, regulatory subunit 1 (p85 alpha) 0.62167 NM_194455 KRIT1 KRIT1, ankyrin repeat containing 0.59477 (j) cytokine - cytokine receptor interaction NM_002089 CXCL2 chemokine (C-X-C motif) ligand 2 0.65945 NM_003810 TNFSF10 tumor necrosis factor (ligand) superfamily, member 10 0.62826 NM_003811 TNFSF9 tumor necrosis factor (ligand) superfamily, member 9 0.64414 NM_031479 INHBE inhibin, beta E 0.60255 (k) The others NM_017915 C12orf48 chromosome 12 open reading frame 48 0.27229 BC021267 KLHL14 kelch-like 14 (Drosophila) 0.45599

1 is a graph illustrating the cytotoxicity of Indeno [1,2,3-c, d) pyrene in human liver cancer cell lines.

Figure 2 is a diagram showing the results of analyzing the gene expression of human liver cancer cell line treated with indeno (1,2,3-c, d) pyrene using a microarray chip.

Claims (9)

Biomarker for confirming the exposure to indeno (1,2,3-c, d) pyrene comprising a gene selected from the following groups: Genebank (Genebank) NM_000606 (C8G, complement component 8, gamma polypeptide), Genebank (Genebank) NM_001429 (EP300, E1A binding protein p300), Genebank (Menebank) NM_003804 (RIPK1, receptor (TNFRSF) -interacting serine-threonine kinase 1), Genebank NM_003806 (HRK, harakiri, BCL2 interacting protein (contains only BH3 domain)), Genebank NM_003901 (SGPL1, sphingosine-1-phosphate lyase 1), Gene Registration Number (Genebank) NM_004049 (BCL2A1, BCL2-related protein A1), Gene Registration Number (Genebank) NM_006437 (PARP4, poly (ADP-ribose) polymerase family, member 4), Gene Registration Number (Genebank) NM_020371 (AVEN, apoptosis , caspase activation inhibitor), genebank NM_022094 (CIDEC, cell death-inducing DFFA-like effector c), genebank NM_022151 (MOAP1, modulator of apoptosis 1), genebank NM_133369 (UNC5A, unc-5 homolog A (C. Elegans)), genes, etc. Genebank NM_138578 (BCL2L1, BCL2-like 1), Gene Registration Number (Genebank) AB040944 (ZSWIM5, zinc finger, SWIM-type containing 5), Gene Registration Number (Genebank) AF144233 (ZMYND8, zinc finger, MYND-type containing 8), Genebank NM_000176 (NR3C1, nuclear receptor subfamily 3, group C, Member 1 (glucocorticoid receptor)), Genebank NM_002180 (IGHMBP2, immunoglobulin mu binding protein 2), Gene registry number (Genebank) NM_006254 (PRKCD, protein kinase c, delta), Genebank NM_016213 (TRIP4, thyroid hormone receptor interactor 4), Genebank NM_019062 (RNF186, ring finger protein 186), gene registration number (Genebank) NM_022482 (GZF1, GDNF-inducible zinc finger protein 1), Genebank NM_033092 (TRIM5, tripartite motif-containing 5), Genebank NM_138287 (DTX3L, deltex 3-like (Drosophila) ), Gene Registration Number (Genebank) NM_145288 (ZNF342, zinc finger prot ein 342), Genebank NM_173548 (ZNF584, zinc finger protein 584), Genebank XM_930521 (ZNF506, zinc finger protein 506), Genebank BX648244 (SPATA13, spermatogenesis associated 13) , Gene Registration Number (Genebank) CR599277 (SERPINB2, serpin peptidase inhibitor, clade B (ovalbumin), member 2), Gene Registration Number (Genebank) NM_000308 (CTSA, cathepsin A), Gene Registration Number (Genebank) NM_001002857 (ANXA2, annexin A2), gene registration number (Genebank) NM_001320 (CSNK2B, casein kinase 2, Beta polypeptide), gene registration number (Genebank) NM_001750 (CAST, calpastatin), gene registration number (Genebank) NM_004152 (OAZ1, ornithine decarboxylase antizyme 1), Gene Registration Number (Genebank) NM_006869 (CENTA1, centaurin, alpha 1), Gene Registration Number (Genebank) NM_014889 (PITRM1, pitrilysin metallopeptidase 1), Gene Registration Number (Genebank) NM_014916 (LMTK2, lemur tyrosine kinase 2) (Genebank) NM_015941 (AT P6V1H, ATPase, h + transporting, Lysosomal 50 / 57kDa, v1 subunit H), Genebank NM_018482 (DDEF1, development and differentiation enhancing factor 1), Genebank NM_018993 (RIN2, Ras and Rab interactor 2), gene registration number (Genebank) NM_032258 (TBC1D3, TBC1 domain family, Member 3), gene registration number (Genebank) NM_058197 (CDKN2A, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)), gene registration number (Genebank) NM_198681 (PLEKHG5, pleckstrin homology domain containing, family G (with RhoGef domain) member 5), Genebank BC002828 (AGGF1, angiogenic factor with G patch and FHA domains 1), Genebank (Genebank) NM_000875 (IGF1R, insulin-like growth factor 1 receptor), genebank (Genebank) NM_001562 (IL18, interleukin 18 (interferon-gamma-inducing factor)), genebank (Genebank) NM_002831 (PTPN6, protein tyrosine phosphatase, non receptor type 6), gene registration number (Geneban) k) NM_003999 (OSMR, oncostatin M receptor), Genebank NM_004624 (VIPR1, vasoactive intestinal peptide receptor 1), Genebank NM_005557 (KRT16, keratin 16 (focal non-epidermolytic palmoplantar keratoderma), Genebank (Genebank) NM_005755 (EBI3, Epstein-Barr virus induced gene 3), Genebank (Genebank) NM_007063 (TBC1D8, TBC1 domain family, member 8 (with GRAM domain)), Genebank (Genebank) NM_016558 ( SCAND1, SCAN domain containing 1), Genebank NM_032965 (CCL15, chemokine (CC motif) ligand 15), Genebank AF343007 (FOXC1, forkhead box C1), Genebank AK074757 (Genebank) ZNF253, zinc finger protein 253), genebank BC063666 (CREB3L2, cAMP responsive element binding protein 3-like 2), genebank NM_001010926 (HES5, hairy and enhancer of split 5 (Drosophila)), Genebank NM_002167 (ID3, inhibitor of DN A binding 3, dominant negative helix-loop-helix protein), Genebank NM_002501 (NFIX, nuclear factor I / X (CCAAT-binding transcription factor)), Genebank NM_003107 (SOX4, SRY ( sex determining region Y) -box 4), Genebank NM_003475 (RASSF7, Ras association (RalGDS / AF-6) domain family 7), Genebank NM_005315 (GSCL, goosecoid-like), Gene Genebank NM_005848 (DENND4A, dENN / MADD domain containing 4A), Gene Registration Number (Genebank) NM_005902 (SMAD3, SMAD family member 3), Genebank NM_006663 (PPP1R13L, protein phosphatase 1, Regulatory (inhibitor) ) subunit 13 like), genebank NM_007005 (TLE4, transducin-like enhancer of split 4 (E (sp1) homolog, Drosophila)), genebank NG_012240 (SIRT4, sirtuin (silent mating type information) regulation 2 homolog) 4 (S. cerevisiae)), Gene Registration Number (Genebank) NM_014368 (LHX6, LIM homeobox 6), Gene Registration Number (Genebank) NM_015481 (ZNF385, zinc finger protein 385), Gene Registration Number (Genebank) NM_016170 (TLX2, T-cell leukemia homeobox) 2), gene registration number (Genebank) NM_021961 (TEAD1, TEA domain family member 1 (SV40 transcriptional enhancer factor)), gene registration number (Genebank) NM_130439 (MXI1, MAX interactor 1), gene registration number (Genebank) NM_152287 (ZNF276 , zinc finger protein 276), gene accession number (Genebank) NM_207305 (FOXD4, forkhead box D4), gene accession number (Genebank) BC035714 (CYP19A1, cytochrome P450, family 19, subfamily A, polypeptide 1), gene accession number (Genebank) ) NM_000603 (NOS3, nitric oxide synthase 3 (endothelial cell)), gene registration number (Genebank) NM_000761 (CYP1A2, cytochrome P450, family 1, subfamily A, polypeptide 2), gene registration number (Genebank) NM_001013660 (FRRS1, ferric- chelate reductase 1), gene accession number (Genebank) NM_004542 (N DUFA3, NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 3,9kDa), gene registration number (Genebank) NM_005390 (PDHA2, pyruvate dehydrogenase (lipoamide) alpha 2), gene registration number (Genebank) NM_005625 (SDCBP, syndecan binding protein (syntenin) )), Gene Registration Number (Genebank) NM_006157 (NELL1, NEL-like 1 (chicken)), Gene Registration Number (Genebank) NM_017460 (CYP3A4, cytochrome P450, family 3, subfamily A, polypeptide 4), Gene Registration Number (Genebank) ) NM_019885 (CYP26B1, cytochrome P450, family 26, subfamily B, polypeptide 1), Genebank NM_022051 (EGLN1, egl nine homolog 1 (C. elegans)), gene registration number (Genebank) NM_032783 (CBR4, carbonyl reductase 4), gene registration number (Genebank) NM_145690 (YWHAZ, tyrosine 3- monooxygenase / tryptophan 5-monooxygenase activation protein, zeta polypeptide), gene registration number (Genebank) ) NM_207352 (CYP4V2, cytochrome P450, family 4, subfamily V, polypeptide 2), gene registration number (Genebank) NM_002047 (GARS, glycyl-tRNA synthetase), gene registration number (Genebank) NM_003344 (UBE2H, ubiquitin-conjugating enzyme E2H UBC8 homolog, yeast)), Genebank NM_003729 (RTCD1, RNA terminal phosphate cyclase domain 1), Genebank NM_005358 (LMO7, LIM domain 7), Genebank NM_006292 (TSG101, tumor susceptibility gene 101), Genebank NM_032673 (PCGF1, polycomb group ring finger 1), Genebank NM_178532 (RNF180, ring finger protein 180), Genebank AF031469 (MR1, major histocompatibility complex, class I-re lated), Genebank BC029781 (C2, complement component 2), Genebank NM_000623 (BDKRB2, bradykinin receptor B2), Genebank NM_001065 (TNFRSF1A, tumor necrosis factor receptor superfamily, member 1A), Genebank NM_001838 (CCR7, chemokine (CC motif) receptor 7), Genebank (Genebank) NM_002119 (HLA-DOA, major histocompatibility complex, class II, DO alpha), Genebank (Genebank) ) NM_002184 (IL6ST, interleukin 6 signal transducer (gp130, oncostatin M receptor)), gene registration number (Genebank) NM_002259 (KLRC1, killer cell lectin-like receptor subfamily C, member 1), gene registration number (Genebank) NM_005018 (PDCD1 , programmed cell death 1), gene registration number (Genebank) NM_006866 (LILRA2, leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 2), gene registration number (Genebank) NM_014314 (DDX58, dEAD (Asp-Glu) -Ala-Asp) box polypeptide 58), gene registration number (G enebank) NM_016232 (IL1RL1, interleukin 1 receptor-like 1), gene accession number (Genebank) NM_018284 (GBP3, guanylate binding protein 3), gene accession number (Genebank) NM_021034 (IFITM3, interferon induced transmembrane protein 3 (1-8U) ), Gene registration number (Genebank) NM_031409 (CCR6, chemokine (CC motif) receptor 6), gene registration number (Genebank) NM_203330 (CD59, cD59 molecule, complement regulatory protein), gene registration number (Genebank) AF078165 (AXIN2, axin 2 (conductin, axil)), Genebank NM_000419 (ITGA2B, integrin, alpha 2b (platelet glycoprotein IIb of IIb / IIIa complex, antigen CD41)), Genebank NM_000758 (CSF2, colony stimulating factor 2 (granulocyte-macrophage)), Genebank (Genebank) NM_001124 (ADM, adrenomedullin), Genebank (Genebank) NM_001381 (DOK1, docking protein 1,62kDa (downstream of tyrosine kinase 1)), Genebank (Genebank) NM_002010 (FGF9, fibroblast growth factor 9 (glia-activating facto r)), Genebank NM_002088 (GRIK5, glutamate receptor, ionotropic, kainate 5), Genebank NM_002222 (ITPR1, inositol 1,4, 5-triphosphate receptor, Type 1), gene registry number (Genebank) NM_002224 (ITPR3, inositol 1,4, 5-triphosphate receptor, Type 3), gene registration number (Genebank) NM_002350 (LYN, v-yes-1 Yamaguchi sarcoma viral related oncogene homolog), gene registration number (Genebank) NM_002561 (P2RX5, purinergic receptor P2X, Ligand-gated ion channel, 5), gene registration number (Genebank) NM_003979 (GPRC5A, g protein-coupled receptor, family C, group 5, Member A), gene registration number (Genebank) NM_004672 (MAP3K6, Mitogen-activated protein kinase kinase kinase 6), gene registration number (Genebank) NM_004843 (IL27RA, interleukin 27 receptor, alpha), gene registration number (Genebank) NM_005297 (MCHR1, Melanin-concentrating hormone receptor 1), gene registration Number (Genebank) NM_022772 (EPS8L2, ePS8-like 2), Gene Registration Number (Genebank) NM_030 571 (NDFIP1, nedd4 family interacting protein 1), Genebank NM_032174 (TOMM40L, Translocase of outer mitochondrial membrane 40 homolog (yeast) -like), Genebank NM_058172 (ANTXR2, anthrax toxin receptor 2) , Genebank NM_153002 (GPR156, g protein-coupled receptor 156), Genebank NM_181501 (ITGA1, integrin, alpha 1), Genebank NM_182665 (RASSF5, Ras association (RalGDS / AF-6) domain family 5), Genebank AB210045 (KIF5A, kinesin family member 5A), Genebank BC010091 (BICD1, Bicaudal D homolog 1 (Drosophila)), Genebank (Genebank) BC027875 (MYO15B, Myosin XVB pseudogene), Gene Registration Number (Genebank) NM_002213 (ITGB5, integrin, Beta 5), Gene Registration Number (Genebank) NM_004735 (LRRFIP1, Leucine rich repeat (in FLII) interacting protein 1), Gene Registration Number Genebank NM_005231 (CTTN, cortactin), Gene Registration Number (Geneban) k) NM_005507 (CFL1, cofilin 1 (non-muscle)), gene accession number (Genebank) NM_006091 (CORO2B, coronin, actin binding protein, 2B), gene accession number (Genebank) NM_006380 (APPBP2, amyloid beta precursor protein (cytoplasmic) tail) binding protein 2), Genebank (Genebank) NM_012144 (DNAI1, dynein, axonemal, intermediate chain 1), Genebank (Genebank) NM_015990 (KLHL5, kelch-like 5 (Drosophila)), Genebank (Genebank) ) NM_018222 (PARVA, parvin, alpha), Gene Registration Number (Genebank) NM_021109 (TMSB4X, Thymosin, Beta 4, X-linked), Gene Registration Number (Genebank) NM_022765 (MICAL1, Microtubule associated monoxygenase, calponin and LIM domain containing 1 ), Gene Registration Number (Genebank) NM_031308 (EPPK1, epiplakin 1), Gene Registration Number (Genebank) NM_033375 (MYO1C, Myosin IC), Gene Registration Number (Genebank) NM_080881 (DBN1, drebrin 1), Gene Registration Number (Genebank) NM_152237 (GAS2L1, growth arrest-specific 2 like 1), Gene Registration Number (Genebank) NM_2 13636 (PDLIM7, pDZ and LIM domain 7 (enigma)), Gene Registration Number (Genebank) NM_000021 (PSEN1, presenilin 1 (Alzheimer disease 3)), Gene Registration Number (Genebank) NM_002034 (FUT5, fucosyltransferase 5 (alpha (1, 3) fucosyltransferase)), Genebank NM_002046 (GAPDH, glyceraldehyde-3-phosphate dehydrogenase), Genebank NM_002392 (MDM2, Mdm2, Transformed 3T3 cell double minute 2, p53 binding protein (mouse)) , Gene Registration Number (Genebank) NM_003333 (UBA52, ubiquitin A-52 residue ribosomal protein fusion product 1), Gene Registration Number (Genebank) NM_004505 (USP6, ubiquitin specific peptidase 6 (Tre-2 oncogene)), Gene Registration Number (Genebank) ) NM_005805 (PSMD14, proteasome (prosome, Macropain) 26S subunit, non-ATPase, 14), Gene Registration Number (Genebank) NM_013396 (USP25, ubiquitin specific peptidase 25), Gene Registration Number (Genebank) NM_017584 (MIOX, Myo-inositol oxygenase), Genebank NM_021009 (UBC, ubiquitin C), gene Genebank NM_032582 (USP32, ubiquitin specific peptidase 32), Gene Registration Number (Genebank) NM_033500 (HK1, hexokinase 1), Gene Registration Number (Genebank) NM_001310 (CREBL2, cAMP responsive element binding protein-like 2), Gene Genebank NM_002166 (ID2, inhibitor of DNA binding 2, dominant negative helix-loop-helix protein), Genebank NM_002622 (PFDN1, prefoldin subunit 1), Genebank NM_003113 (SP100, sP100 nuclear antigen, Genebank NM_005419 (STAT2, signal transducer and activator of transcription 2,113kDa), Genebank NM_005526 (HSF1, heat shock transcription factor 1), Genebank NM_005920 ( MEF2D, Myocyte enhancer factor 2D, Genebank NM_014212 (HOXC11, homeobox C11), Genebank NM_014423 (AFF4, aF4 / FMR2 family, Member 4), Genebank NM_015106 (RAD54L2 , RAD54-like 2 (S. cerevisiae)), Genebank NM_017422 (CALML5, calmodulin-like 5), Genebank NM_032292 (GON4L, gon-4-like (C. elegans)), Genebank NM_134424 (RAD52, RAD52 homolog (S. cerevisiae)), Genebank NM_144631 (ZNF513, zinc finger protein 513), Genebank NM_001012334 (MDK, Midkine (neurite growth-promoting factor 2)), gene Genebank NM_001761 (CCNF, cyclin F), Genebank (Genebank) NM_001789 (CDC25A, cell division cycle 25 homolog A (S. pombe)), Genebank (Genebank) NM_002823 (PTMA, prothymosin, alpha ( gene sequence 28)), genebank NM_007295 (BRCA1, Breast cancer 1, early onset), genebank NM_014221 (MTCP1, Mature T-cell proliferation 1), genebank NM_014708 ( KNTC1, kinetochore associated 1), Genebank NM_015097 (CLASP2, cytoplasmic linker associated protein 2), heredity Registration Number (Genebank) NM_018151 (RIF1, RAP1 interacting factor homolog (yeast)), gene registration number (Genebank) AL117645 (MED28, Mediator of RNA polymerase II transcription, subunit 28 homolog (S. cerevisiae)), Genebank BC042297 (UBTF, upstream binding transcription factor, RNA polymerase I), Genebank NM_000449 (RFX5, Regulatory factor X, 5 (influences HLA class II expression)), Gene Registration Number (Genebank) NM_001032372 (ZNF226, zinc finger protein 226), gene registration number (Genebank) NM_003216 (TEF, Thyrotrophic embryonic factor), gene accession number (Genebank) NM_003411 (ZFY, zinc finger protein, Y-linked), gene registration Number (Genebank) NM_003865 (HESX1, hESX homeobox 1), Gene Registration Number (Genebank) NM_003920 (TIMELESS, Timeless homolog (Drosophila)), Gene Registration Number (Genebank) NM_005254 (GABPB2, gA binding protein transcription factor, Beta subunit 2) , Gene Registration Number (Genebank) NM_006089 (SCML2, sex comb on midleg-like 2 (Drosophila)), Gene Registration Number (Genebank) NM_006454 (MXD4, MAX dimerization protein 4), Gene Registration Number (Genebank) NM_006530 (YEATS4, YEATS domain containing 4), gene registration number Genebank NM_013249 (ZNF214, zinc finger protein 214), Genebank NM_014288 (ITGB3BP, integrin beta 3 binding protein (beta3-endonexin)), Genebank NM_016578 (RSF1, Remodeling and spacing factor 1 ), Gene registration number (Genebank) NM_018645 (HES6, hairy and enhancer of split 6 (Drosophila)), gene registration number (Genebank) NM_020062 (SLC2A4RG, sLC2A4 regulator), gene registration number (Genebank) NM_021148 (ZNF273, zinc finger protein 273), Genebank NM_021269 (ZNF708, zinc finger protein 708), Genebank NM_025027 (ZNF606, zinc finger protein 606), Genebank NM_144566 (ZNF700, zinc finger protein 700) Gene Registration Number (Genebank) NM_175910 (ZNF493, zinc finger protein 493), Gene Registration Number (Genebank) NM_198968 (DZIP1, dAZ interacting protein 1), Gene Registration Number (Genebank) Y09321 (TAF4B, TAF4b RNA polymerase II, TATA box binding protein (TBP)-associated factor, 105 kDa) , Genebank NM_000251 (MSH2, MutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)), Genebank NM_001039651 (C6orf26, chromosome 6 open reading frame 26), Genebank NM_001071 (TYMS, Thymidylate synthetase), Genebank NM_002485 (NBN, nibrin), Gene Genebank NM_002592 (PCNA, proliferating cell nuclear antigen), Genebank NM_004219 (PTTG1, pituitary tumor-transforming 1), Genebank NM_005427 (TP73, Tumor protein p73), Gene Registration Number (Genebank) NM_005441 (CHAF1B, chromatin assembly factor 1, subunit B (p60)), gene registration number (Genebank) NM_005484 (PARP2, poly (ADP-ribose) polymerase family, Member 2), gene registration number (Genebank) NM_016218 ( POLK, polymerase (DNA directed) kappa), genebank (Genebank) BC048985 (TAF15, TAF15 RNA polymerase II, TATA box binding protein (TBP) -associated factor, 68kDa), genebank (Genebank) NM_001007101 (ZNF484, zinc finger protein 484), Genebank NM_002383 (MA Z, MYC-associated zinc finger protein (purine-binding transcription factor), Genebank NM_003316 (TTC3, Tetratricopeptide repeat domain 3), Genebank NM_003410 (ZFX, zinc finger protein, X-linked ), Gene registration number (Genebank) NM_005060 (RORC, RAR-related orphan receptor C), gene registration number (Genebank) NM_006963 (ZNF22, zinc finger protein 22 (KOX 15)), gene registration number (Genebank) NM_014898 (ZFP30, zinc finger protein 30 homolog (mouse), Genebank NM_016019 (LUC7L2, LUC7-like 2 (S. cerevisiae)), Gene Registration Number (Genebank) NM_017661 (SUHW4, suppressor of hairy wing homolog 4 (Drosophila)), Gene Registration Number (Genebank) NM_021178 (CCNB1IP1, cyclin B1 interacting protein 1), Gene Registration Number (Genebank) NM_030899 ( ZNF323, zinc finger protein 323, Genebank NM_032268 (ZNRF1, zinc and ring finger 1), Genebank NM_033089 (ZCCHC3, zinc finger, cCHC domain containing 3), Genebank (Genebank) NM_152355 (ZNF441, zinc finger protein 441), Genebank (Genebank) NM_181756 (ZNF233, zinc finger protein 233), Genebank (Genebank) NM_182515 (ZNF714, zinc finger protein 714), Genebank AK131529 (Genebank) AATK, apoptosis-associated tyrosine kinase, genebank NM_000289 (PFKM, phosphofructokinase, Muscle), genebank NM_000553 (WRN, Werner syndrome), genebank NM_001786 (CDC2, cell division cycle 2, g1 to S and G2 to M), Gene Registration Number (Genebank) NM_001813 (CENPE, centromere protein E, 312 kDa), Gene Registration Number (Genebank) NM_003579 (RAD54L, RAD54-like (S. cerevisiae)), Gene Registration Number (Genebank) NM_005964 (MYH10, Myosin, heavy chain 10, non-muscle), gene registration number (Genebank) NM_006306 (SMC1A, structural maintenance of chromosomes 1A), gene registration number (Genebank) NM_013257 (SGK3, serum / glucocorticoid regulated kinase family, Member 3), gene registration number ( Genebank) NM_014616 (ATP11B, aTPase, class VI, Type 11B), Gene Registration Number (Genebank) NM_015512 (DNAH1, dynein, axonemal, heavy chain 1), Gene Registration Number (Genebank) NM_016350 (NIN, ninein (GSK3B interacting protein) Genebank NM_018183 (SBNO1, strawberry notch homolog 1 (Drosophila)), Genebank NM_020159 (SMARCAD1, sWI / SNF-related, Matrix-associated actin-dependent regulator of chromatin, subfamily a, containing DEAD / H box 1), Gene Accession Number (Genebank) NM_024320 (ATAD4 , aTPase family, aAA domain containing 4), Genebank NM_024594 (PANK3, pantothenate kinase 3), Genebank NM_033151 (ABCC11, aTP-binding cassette, sub-family C (CFTR / MRP), Member 11), Gene Registration Number (Genebank) NM_182802 (MCM8, Minichromosome maintenance complex component 8), Gene Registration Number (Genebank) NM_207578 (PRKACB, protein kinase, cAMP-dependent, catalytic, Beta), Gene Registration Number (Genebank) NR_002451 (ABCA11, aTP-binding cassette, sub-family A (ABC1), Member 11 (pseudogene)), gene registration number (Genebank) AF042838 (MAP3K1, Mitogen-activated protein kinase kinase kinase 1), gene registration number (Genebank) AL117400 (PASK, pAS domain containing serine / threonine kinase), gene registration number (Genebank) NM_000221 (KHK, ketohexokinase (fructokinase)), gene registration number (Genebank) NM_001005735 (CHEK2, cHK2 checkpoint homolog (S. pombe), Genebank NM_001626 (AKT2, v-akt murine thymoma viral oncogene homolog 2), Genebank NM_001826 (CKS1B, cDC28 protein kinase regulatory subunit 1B), Genebank NM_002758 (MAP2K6, Mitogen-activated protein kinase kinase 6), gene registration number (Genebank) NM_005400 (PRKCE, protein kinase C, epsilon), gene registration number (Genebank) NM_006716 (DBF4, dBF4 homolog (S. cerevisiae)), gene registration Genebank NM_014215 (INSRR, insulin receptor-related receptor), Genebank NM_023110 (FGFR1, fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, pfeiffer syndrome), Genebank NM_032246 (RKHD3, Ring finger and KH domain containing 3), Gene Registration Number (Genebank) NM_052987 (CDK10, cyclin-dependent kinase (CDC2-like) 10), Gene Registration Number (Genebank) NM_001005526 (SF3B1, splicing factor 3b, subunit 1,155 kDa), Genebank NM_002138 (HNRPD) , heterogeneous nuclear ribonucleoprotein D (AU-rich element RNA binding protein 1,37kDa), gene registration number (Genebank) NM_003400 (XPO1, exportin 1 (CRM1 homolog, Yeast)), gene registration number (Genebank) NM_004814 (WDR57, WD repeat domain 57 (U5 snRNP specific), Genebank NM_005033 (EXOSC9, exosome component 9), Genebank NM_006527 (SLBP, stem-loop (histone) binding protein), Genebank (Genebank) ) NM_006638 (RPP40, Ribonuclease P 40kDa subunit), gene registration number (Genebank) NM_006805 (HNRPA0, heterogeneous nuclear ribonucleoprotein A0), gene registration number (Genebank) NM_014953 (DIS3, dIS3 mitotic control homolog (S. cerevisiae)), Genebank NM_032361 (THOC3, THO complex 3), Genebank NM_152292 (RG9MTD2, RNA (guanine-9-) methyltransferase domain containing 2), Genebank AF090937 (SORBS2, sorbin and SH3 domain containing 2), Genebank (Genebank) NM_000583 (GC, group-specific component (vitamin D binding protein)), Genebank (Genebank) NM_001001290 (SLC2A9, solute carrier family 2 (facilitated glucose) transporter), Member 9), Genebank NM_001045 (SLC6A4, solute carrier family 6 (neurotransmitter transporter, serotonin, Member 4), Genebank NM_003366 (UQCRC2, ubiquinol-cytochrome c reductase core protein II) , Genebank NM_004896 (VPS26A, vacuolar protein sorting 26 homolog A (S.pombe)), Genebank (Genebank) NM_006028 (HTR3B, 5-hydroxytryptamine (serotonin) receptor 3B), Genebank (Genebank) NM_006359 (SLC9A6, solute carrier family 9 (s odium / hydrogen exchanger), Member 6), Genebank NM_006416 (SLC35A1, solute carrier family 35 (CMP-sialic acid transporter), Member A1), Genebank NM_006544 (EXOC5, exocyst complex component 5 ), Gene registration number (Genebank) NM_014229 (SLC6A11, solute carrier family 6 (neurotransmitter transporter, gABA), Member 11), gene registration number (Genebank) NM_016057 (COPZ1, coatomer protein complex, subunit zeta 1), gene registration number ( Genebank) NM_016320 (NUP98, nucleoporin 98kDa), Genebank Number (Genebank) NM_018155 (SLC25A36, solute carrier family 25, Member 36), Genebank Number (Genebank) NM_175623 (RAB3IP, RAB3A interacting protein (rabin3), Gene Registration Number (Genebank) AF256215 (ARNTL2, aryl hydrocarbon receptor nuclear translocator-like 2), gene accession number (Genebank) BC041387 (MCTP2, Multiple C2 domains, Transmembrane 2), gene accession number (Genebank) NM_000506 (F2, coagulation factor II (thrombin) )), Gene registration number (Genebank) NM_000820 (GAS6, growth arrest-specific 6), Gene Registration Number (Genebank) NM_002317 (LOX, Lysyl oxidase), Gene Registration Number (Genebank) NM_002834 (PTPN11, protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome) 1)), Gene Registration Number (Genebank) NM_003546 (HIST1H4L, histone cluster 1, h4l), Gene Registration Number (Genebank) NM_004311 (ARL3, aDP-ribosylation factor-like 3), Gene Registration Number (Genebank) NM_006203 (PDE4D, phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, drosophila), genebank NM_012096 (APPL1, adapter protein, phosphotyrosine interaction, pH domain and leucine zipper containing 1), genebank NM_012309 (SHANK2) , sH3 and multiple ankyrin repeat domains 2), Genebank NM_012425 (RSU1, Ras suppressor protein 1), Genebank NM_015547 (ACOT11, acyl-CoA thioesterase 11), Genebank NM_016022 (APH1A, anterior pharynx defec tive 1 homolog A (C. elegans)), Genebank NM_024718 (C9orf86, chromosome 9 open reading frame 86), Genebank NM_080651 (THRAP6, Thyroid hormone receptor associated protein 6), Genebank NM_181523 (PIK3R1, phosphoinositide-3-kinase, Regulatory subunit 1 (p85 alpha)), gene accession number (Genebank) NM_194455 (KRIT1, kRIT1, ankyrin repeat containing), gene accession number (Genebank) NM_002089 (CXCL2, chemokine (CXC motif) ligand 2) , Genebank (Genebank) NM_003810 (TNFSF10, Tumor necrosis factor (ligand) superfamily, Member 10), Genebank (Genebank) NM_003811 (TNFSF9, Tumor necrosis factor (ligand) superfamily, Member 9), Gene accession number (Genebank) ) NM_031479 (INHBE, inhibin, Beta E), Genebank (Genebank) NM_017915 (C12orf48, chromosome 12 open reading frame 48), Genebank (Genebank) BC021267 (KLHL14, kelch-like 14 (Drosophila)) The biomarker of claim 1, wherein the following gene is increased in expression by exposure to indeno (1,2,3-c, d) pyrene: Genebank (Genebank) NM_000606 (C8G, complement component 8, gamma polypeptide), Genebank (Genebank) NM_001429 (EP300, e1A binding protein p300), Genebank (Menebank) NM_003804 (RIPK1, Receptor (TNFRSF) -interacting serine-threonine kinase 1), Genebank NM_003806 (HRK, harakiri, BCL2 interacting protein (contains only BH3 domain)), Genebank NM_003901 (SGPL1, sphingosine-1-phosphate lyase 1), Gene Registration Number (Genebank) NM_004049 (BCL2A1, BCL2-related protein A1), Gene Registration Number (Genebank) NM_006437 (PARP4, poly (ADP-ribose) polymerase family, member 4), Gene Registration Number (Genebank) NM_020371 (AVEN, apoptosis , caspase activation inhibitor), genebank NM_022094 (CIDEC, cell death-inducing DFFA-like effector c), genebank NM_022151 (MOAP1, Modulator of apoptosis 1), genebank NM_133369 (UNC5A, unc-5 homolog A (C. Elegans)), genes, etc. (Genebank) NM_138578 (BCL2L1, BCL2-like 1), Gene Registration Number (Genebank) AB040944 (ZSWIM5, zinc finger, sWIM-type containing 5), Gene Registration Number (Genebank) AF144233 (ZMYND8, zinc finger, MYND- type containing 8), gene registration number (Genebank) NM_000176 (NR3C1, nuclear receptor subfamily 3, group C, Member 1 (glucocorticoid receptor)), gene registration number (Genebank) NM_002180 (IGHMBP2, immunoglobulin mu binding protein 2), gene registration Number (Genebank) NM_006254 (PRKCD, protein kinase c, delta), gene registration number (Genebank) NM_016213 (TRIP4, Thyroid hormone receptor interactor 4), gene registration number (Genebank) NM_019062 (RNF186, Ring finger protein 186), gene registration Genebank NM_022482 (GZF1, gDNF-inducible zinc finger protein 1), Gene Registration Number (Genebank) NM_033092 (TRIM5, Tripartite motif-containing 5), Genebank Number NM_138287 (DTX3L, deltex 3-like (Drosophila) ), Gene Registration Number (Genebank) NM_145288 (ZNF342, zinc finger prot ein 342), Genebank NM_173548 (ZNF584, zinc finger protein 584), Genebank XM_930521 (ZNF506, zinc finger protein 506), Genebank BX648244 (SPATA13, spermatogenesis associated 13 ), Genebank Number CR599277 (SERPINB2, serpin peptidase inhibitor, clade B (ovalbumin), Member 2), Genebank Number (Genebank) NM_000308 (CTSA, cathepsin A), Genebank Number (Menebank) NM_001002857 (ANXA2, annexin A2), Genebank NM_001320 (CSNK2B, casein kinase 2, Beta polypeptide), Genebank NG_001750 (CAST, calpastatin), Genebank NM_004152 (OAZ1, ornithine decarboxylase antizyme 1) , Gene Registration Number (Genebank) NM_006869 (CENTA1, centaurin, alpha 1), Gene Registration Number (Genebank) NM_014889 (PITRM1, pitrilysin metallopeptidase 1), Gene Registration Number (Genebank) NM_014916 (LMTK2, Lemur tyrosine kinase 2) Number (Genebank) NM_015941 (AT P6V1H, aTPase, h + transporting, Lysosomal 50 / 57kDa, v1 subunit H), Genebank NM_018482 (DDEF1, development and differentiation enhancing factor 1), Genebank NM_018993 (RIN2, Ras and Rab interactor 2), gene registration number (Genebank) NM_032258 (TBC1D3, TBC1 domain family, Member 3), gene registration number (Genebank) NM_058197 (CDKN2A, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)), gene registration number (Genebank) NM_198681 (PLEKHG5, pleckstrin homology domain containing, family G (with RhoGef domain) member 5), Genebank BC002828 (AGGF1, angiogenic factor with G patch and FHA domains 1), Genebank (Genebank) NM_000875 (IGF1R, insulin-like growth factor 1 receptor), Genebank NM_001562 (IL18, interleukin 18 (interferon-gamma-inducing factor)), Gene Accession Number (Genebank) NM_002831 (PTPN6, protein tyrosine phosphatase, non-receptor type 6), gene registration number (Geneba) nk) NM_003999 (OSMR, oncostatin M receptor), Genebank NM_004624 (VIPR1, vasoactive intestinal peptide receptor 1), Genebank NM_005557 (KRT16, keratin 16 (focal non-epidermolytic palmoplantar keratoderma), Genebank (Genebank) NM_005755 (EBI3, epstein-Barr virus induced gene 3), Genebank (Genebank) NM_007063 (TBC1D8, TBC1 domain family, member 8 (with GRAM domain)), Genebank (Genebank) NM_016558 ( SCAND1, sCAN domain containing 1), Genebank NM_032965 (CCL15, chemokine (CC motif) ligand 15), Genebank AF343007 (FOXC1, forkhead box C1), Genebank AK074757 (Genebank) ZNF253, zinc finger protein 253), genebank BC063666 (CREB3L2, cAMP responsive element binding protein 3-like 2), genebank NM_001010926 (HES5, hairy and enhancer of split 5 (Drosophila)), Genebank NM_002167 (ID3, inhibitor of DN A binding 3, dominant negative helix-loop-helix protein), Genebank NM_002501 (NFIX, nuclear factor I / X (CCAAT-binding transcription factor)), Genebank NM_003107 (SOX4, sRY ( sex determining region Y) -box 4), Genebank NM_003475 (RASSF7, Ras association (RalGDS / AF-6) domain family 7), Genebank NM_005315 (GSCL, goosecoid-like), Gene Genebank NM_005848 (DENND4A, dENN / MADD domain containing 4A), Genebank NM_005902 (SMAD3, sMAD family member 3), Genebank NM_006663 (PPP1R13L, protein phosphatase 1, Regulatory (inhibitor) subunit 13 like), Genebank NM_007005 (TLE4, Transducin-like enhancer of split 4 (E (sp1) homolog, Drosophila)), Genebank NM_012240 (SIRT4, sirtuin (silent mating type information) regulation 2 homolog) 4 (S. cerevisiae)), Genebank NM_014368 (LHX6, LIM homeobox 6), Genebank NM_015481 (ZNF385, zinc finger protein 385), Genebank NM_016170 (TLX2, T-cell leukemia homeobox 2), gene registration number (Genebank) NM_021961 (TEAD1, TEA domain family member 1 (SV40 transcriptional enhancer factor)), gene registration number (Genebank) NM_130439 (MXI1, MAX interactor 1), gene registration number (Genebank) NM_152287 (ZNF276 , zinc finger protein 276), gene accession number (Genebank) NM_207305 (FOXD4, forkhead box D4), gene accession number (Genebank) BC035714 (CYP19A1, cytochrome P450, family 19, subfamily A, polypeptide 1), gene accession number (Genebank) ) NM_000603 (NOS3, nitric oxide synthase 3 (endothelial cell)), gene registration number (Genebank) NM_000761 (CYP1A2, cytochrome P450, family 1, subfamily A, polypeptide 2), gene registration number (Genebank) NM_001013660 (FRRS1, ferric- chelate reductase 1), gene accession number (Genebank) NM_004542 (ND UFA3, nADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 3,9kDa), gene registration number (Genebank) NM_005390 (PDHA2, pyruvate dehydrogenase (lipoamide) alpha 2), gene registration number (Genebank) NM_005625 (SDCBP, syndecan binding protein (syntenin) )), Gene Registration Number (Genebank) NM_006157 (NELL1, nEL-like 1 (chicken)), Gene Registration Number (Genebank) NM_017460 (CYP3A4, cytochrome P450, family 3, subfamily A, polypeptide 4), Gene Registration Number (Genebank) ) NM_019885 (CYP26B1, cytochrome P450, family 26, subfamily B, polypeptide 1), Genebank NM_022051 (EGLN1, egl nine homolog 1 (C. elegans)), gene registration number (Genebank) NM_032783 (CBR4, carbonyl reductase 4), gene registration number (Genebank) NM_145690 (YWHAZ, Tyrosine 3-monooxygenase / tryptophan 5-monooxygenase activation protein, zeta polypeptide), gene registration number (Genebank) ) NM_207352 (CYP4V2, cytochrome P450, family 4, subfamily V, polypeptide 2), gene registration number (Genebank) NM_002047 (GARS, glycyl-tRNA synthetase), gene registration number (Genebank) NM_003344 (UBE2H, ubiquitin-conjugating enzyme E2H UBC8 homolog, yeast)), Genebank NM_003729 (RTCD1, RNA terminal phosphate cyclase domain 1), Genebank NM_005358 (LMO7, LIM domain 7), Genebank NM_006292 (TSG101, Tumor susceptibility gene 101), Genebank NM_032673 (PCGF1, polycomb group ring finger 1), Genebank NM_178532 (RNF180, Ring finger protein 180), Genebank AF031469 (MR1, Major histocompatibility complex, class I- re lated), Genebank BC029781 (C2, complement component 2), Genebank NM_000623 (BDKRB2, Bradykinin receptor B2), Genebank NM_001065 (TNFRSF1A, Tumor necrosis factor receptor superfamily, Member 1A), Genebank NM_001838 (CCR7, chemokine (CC motif) receptor 7), Genebank (Genebank) NM_002119 (HLA-DOA, Major histocompatibility complex, class II, dO alpha), Genebank (Genebank) ) NM_002184 (IL6ST, interleukin 6 signal transducer (gp130, oncostatin M receptor)), gene registration number (Genebank) NM_002259 (KLRC1, killer cell lectin-like receptor subfamily C, Member 1), gene registration number (Genebank) NM_005018 (PDCD1 , programmed cell death 1), Genebank NM_006866 (LILRA2, Leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 2), Genebank NM_014314 (DDX58, dEAD (Asp-Glu -Ala-Asp) box polypeptide 58), gene registration number (Ge nebank) NM_016232 (IL1RL1, interleukin 1 receptor-like 1), gene accession number (Genebank) NM_018284 (GBP3, guanylate binding protein 3), gene accession number (Genebank) NM_021034 (IFITM3, interferon induced transmembrane protein 3 (1-8U) ), Gene registration number (Genebank) NM_031409 (CCR6, chemokine (CC motif) receptor 6), gene registration number (Genebank) NM_203330 (CD59, cD59 molecule, complement regulatory protein), gene registration number (Genebank) AF078165 (AXIN2, axin 2 (conductin, axil)), Genebank NM_000419 (ITGA2B, integrin, alpha 2b (platelet glycoprotein IIb of IIb / IIIa complex, antigen CD41)), Genebank NM_000758 (CSF2, colony stimulating factor 2 (granulocyte-macrophage)), Genebank (Genebank) NM_001124 (ADM, adrenomedullin), Genebank (Genebank) NM_001381 (DOK1, docking protein 1,62kDa (downstream of tyrosine kinase 1)), Genebank (Genebank) NM_002010 (FGF9, fibroblast growth factor 9 (glia-activating facto r)), Genebank NM_002088 (GRIK5, glutamate receptor, ionotropic, kainate 5), Genebank NM_002222 (ITPR1, inositol 1,4, 5-triphosphate receptor, Type 1), gene registry number (Genebank) NM_002224 (ITPR3, inositol 1,4, 5-triphosphate receptor, Type 3), gene registration number (Genebank) NM_002350 (LYN, v-yes-1 Yamaguchi sarcoma viral related oncogene homolog), gene registration number (Genebank) NM_002561 (P2RX5, purinergic receptor P2X, Ligand-gated ion channel, 5), gene registration number (Genebank) NM_003979 (GPRC5A, g protein-coupled receptor, family C, group 5, Member A), gene registration number (Genebank) NM_004672 (MAP3K6, Mitogen-activated protein kinase kinase kinase 6), gene registration number (Genebank) NM_004843 (IL27RA, interleukin 27 receptor, alpha), gene registration number (Genebank) NM_005297 (MCHR1, Melanin-concentrating hormone receptor 1), gene registration Number (Genebank) NM_022772 (EPS8L2, ePS8-like 2), Gene Registration Number (Genebank) NM_0305 71 (NDFIP1, nedd4 family interacting protein 1), Genebank NM_032174 (TOMM40L, Translocase of outer mitochondrial membrane 40 homolog (yeast) -like), Genebank NM_058172 (ANTXR2, anthrax toxin receptor 2) , Genebank NM_153002 (GPR156, g protein-coupled receptor 156), Genebank NM_181501 (ITGA1, integrin, alpha 1), Genebank NM_182665 (RASSF5, Ras association (RalGDS / AF-6) domain family 5), Genebank AB210045 (KIF5A, kinesin family member 5A), Genebank BC010091 (BICD1, Bicaudal D homolog 1 (Drosophila)), Genebank (Genebank) BC027875 (MYO15B, Myosin XVB pseudogene), Gene Registration Number (Genebank) NM_002213 (ITGB5, integrin, Beta 5), Gene Registration Number (Genebank) NM_004735 (LRRFIP1, Leucine rich repeat (in FLII) interacting protein 1), Gene Registration Number Genebank NM_005231 (CTTN, cortactin), Gene Registration Number (Genebank) ) NM_005507 (CFL1, cofilin 1 (non-muscle)), Gene Registration Number (Genebank) NM_006091 (CORO2B, coronin, actin binding protein, 2B), Gene Registration Number (Genebank) NM_006380 (APPBP2, amyloid beta precursor protein (cytoplasmic tail) ) binding protein 2), gene registration number (Genebank) NM_012144 (DNAI1, dynein, axonemal, intermediate chain 1), gene registration number (Genebank) NM_015990 (KLHL5, kelch-like 5 (Drosophila)), gene registration number (Genebank) NM_018222 (PARVA, parvin, alpha), Gene Registration Number (Genebank) NM_021109 (TMSB4X, Thymosin, Beta 4, X-linked), Gene Registration Number (Genebank) NM_022765 (MICAL1, Microtubule associated monoxygenase, calponin and LIM domain containing 1) , Gene Registration Number (Genebank) NM_031308 (EPPK1, epiplakin 1), Gene Registration Number (Genebank) NM_033375 (MYO1C, Myosin IC), Gene Registration Number (Genebank) NM_080881 (DBN1, drebrin 1), Gene Registration Number (Genebank) NM_152237 (GAS2L1, growth arrest-specific 2 like 1), Gene Registration Number (Genebank) NM_2 13636 (PDLIM7, pDZ and LIM domain 7 (enigma)), Gene Registration Number (Genebank) NM_000021 (PSEN1, presenilin 1 (Alzheimer disease 3)), Gene Registration Number (Genebank) NM_002034 (FUT5, fucosyltransferase 5 (alpha (1, 3) fucosyltransferase)), Genebank NM_002046 (GAPDH, glyceraldehyde-3-phosphate dehydrogenase), Genebank NM_002392 (MDM2, Mdm2, Transformed 3T3 cell double minute 2, p53 binding protein (mouse)) , Gene Registration Number (Genebank) NM_003333 (UBA52, ubiquitin A-52 residue ribosomal protein fusion product 1), Gene Registration Number (Genebank) NM_004505 (USP6, ubiquitin specific peptidase 6 (Tre-2 oncogene)), Gene Registration Number (Genebank) ) NM_005805 (PSMD14, proteasome (prosome, Macropain) 26S subunit, non-ATPase, 14), Gene Registration Number (Genebank) NM_013396 (USP25, ubiquitin specific peptidase 25), Gene Registration Number (Genebank) NM_017584 (MIOX, Myo-inositol oxygenase), Genebank NM_021009 (UBC, ubiquitin C), gene Genebank NM_032582 (USP32, ubiquitin specific peptidase 32), Gene Registration Number (Genebank) NM_033500 (HK1, hexokinase 1), Gene Registration Number (Genebank) NM_001310 (CREBL2, cAMP responsive element binding protein-like 2), Gene Genebank NM_002166 (ID2, inhibitor of DNA binding 2, dominant negative helix-loop-helix protein), Genebank NM_002622 (PFDN1, prefoldin subunit 1), Genebank NM_003113 (SP100, sP100 nuclear antigen, Genebank NM_005419 (STAT2, signal transducer and activator of transcription 2,113kDa), Genebank NM_005526 (HSF1, heat shock transcription factor 1), Genebank NM_005920 ( MEF2D, Myocyte enhancer factor 2D, Genebank NM_014212 (HOXC11, homeobox C11), Genebank NM_014423 (AFF4, aF4 / FMR2 family, Member 4), Genebank NM_015106 (RAD54L2 , RAD54-like 2 (S. cerevisiae)), gene registration number (Genebank) NM_017422 (CALML5, calmodulin-like 5), gene registration number (Genebank) NM_032292 (GON4L, gon-4-like (C. elegans)), gene registration number (Genebank) NM_134424 ( RAD52, RAD52 homolog (S. cerevisiae), Genebank NM_144631 (ZNF513, zinc finger protein 513) The biomarker of claim 1, wherein the following genes are reduced in expression by exposure to indeno (1,2,3-c, d) pyrene: Genebank (Genebank) NM_001012334 (MDK, Midkine (neurite growth-promoting factor 2)), Genebank (Genebank) NM_001761 (CCNF, cyclin F), Genebank (Menebank) NM_001789 (CDC25A, cell division cycle 25 homolog A (S. pombe)), Genebank NM_002823 (PTMA, prothymosin, alpha (gene sequence 28)), Genebank NM_007295 (BRCA1, Breast cancer 1, early onset), Gene accession number ( Genebank) NM_014221 (MTCP1, Mature T-cell proliferation 1), Genebank NM_014708 (KNTC1, kinetochore associated 1), Genebank NM_015097 (CLASP2, cytoplasmic linker associated protein 2), Gene accession number ( Genebank) NM_018151 (RIF1, RAP1 interacting factor homolog (yeast), Genebank AL117645 (MED28, Mediator of RNA polymerase II transcription, subunit 28 homolog (S. cerevisiae)), Gene accession number (Genebank) BC042297 ( UBTF, upstream binding transcription factor, RNA polymerase I), Genebank NM_000449 (RFX5, Regulatory factor X, 5 (influences HLA class II expression)), Genebank NM_001032372 (ZNF226, zinc finger protein 226), Genebank NM_003216 (TEF, Thyrotrophic embryonic factor, Genebank NM_003411 (ZFY, zinc finger protein, Y-linked), Genebank NM_003865 (HESX1, hESX homeobox 1), Genebank NM_003920 (TIMELESS, Timeless homolog (Drosophila), Genebank NM_005254 (GABPB2, gA binding protein transcription factor, Beta subunit 2), Genebank NM_006089 (SCML2, sex comb on midleg-like 2 (Drosophila)), gene Genebank NM_006454 (MXD4, MAX dimerization protein 4), Genebank NM_006530 (YEATS4, YEATS domain containing 4), Genebank NM_013249 (ZNF214, zinc finger protein 214), Gene Registration Number (Genebank) NM_014288 (ITGB3BP, integrin bet a 3 binding protein (beta3-endonexin)), Genebank NM_016578 (RSF1, Remodeling and spacing factor 1), Genebank NM_018645 (HES6, hairy and enhancer of split 6 (Drosophila)), gene Genebank NM_020062 (SLC2A4RG, sLC2A4 regulator), Genebank NM_021148 (ZNF273, zinc finger protein 273), Genebank NM_021269 (ZNF708, zinc finger protein 708), Gene registry number (Genebank) ) NM_025027 (ZNF606, zinc finger protein 606), Genebank (Genebank) NM_144566 (ZNF700, zinc finger protein 700), Genebank (Genebank) NM_175910 (ZNF493, zinc finger protein 493), Gene accession number (Genebank) NM_198968 (DZIP1, dAZ interacting protein 1), Genebank Y09321 (TAF4B, TAF4b RNA polymerase II, TATA box binding protein (TBP) -associated factor, 105 kDa), Genebank NM_000251 (MSH2, MutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)), Genebank NM_001039651 (C6orf26, chromosome 6 open reading frame 26), Genebank NM_001071 (TYMS, Thymidylate synthetase), Genebank NM_002485 (NBN, nibrin), Gene Genebank NM_002592 (PCNA, proliferating cell nuclear antigen), Genebank NM_004219 (PTTG1, pituitary tumor-transforming 1), Genebank NM_005427 (TP73, Tumor protein p73), Gene registration Number (Genebank) NM_005441 (CHAF1B, chromatin assembly factor 1, subunit B (p60)), gene registration number (Genebank) NM_005484 (PARP2, poly (ADP-ribose) polymerase family, Member 2), gene registration number (Genebank) NM_016218 (POLK, polymerase (DNA directed) kappa), Genebank BC048985 (TAF15, TAF15 RNA polymerase II, TATA box binding protein (TBP) -associated factor, 68kDa), Genebank (Menebank) NM_001007101 (ZNF484, zinc finger protein 484), Genebank NM_002383 ( MAZ, MYC-associated zinc finger protein (purine-binding transcription factor), Genebank NM_003316 (TTC3, Tetratricopeptide repeat domain 3), Genebank NM_003410 (ZFX, zinc finger protein, X-linked ), Gene registration number (Genebank) NM_005060 (RORC, RAR-related orphan receptor C), gene registration number (Genebank) NM_006963 (ZNF22, zinc finger protein 22 (KOX 15)), gene registration number (Genebank) NM_014898 (ZFP30, zinc finger protein 30 homolog (mouse), Genebank NM_016019 (LUC7L2, LUC7-like 2 (S. cerevisiae)), Gene Registration Number (Genebank) NM_017661 (SUHW4, suppressor of hairy wing homolog 4 (Drosophila)), Gene Registration Number (Genebank) NM_021178 (CCNB1IP1, cyclin B1 interacting protein 1), Gene Registration Number (Genebank) NM_030899 ( ZNF323, zinc finger protein 323, Genebank NM_032268 (ZNRF1, zinc and ring finger 1), Genebank NM_033089 (ZCCHC3, zinc finger, cCHC domain containing 3), Genebank (Genebank) NM_152355 (ZNF441, zinc finger protein 441), Genebank (Genebank) NM_181756 (ZNF233, zinc finger protein 233), Genebank (Genebank) NM_182515 (ZNF714, zinc finger protein 714), Genebank AK131529 (Genebank) AATK, apoptosis-associated tyrosine kinase, genebank NM_000289 (PFKM, phosphofructokinase, Muscle), genebank NM_000553 (WRN, Werner syndrome), genebank NM_001786 (CDC2, cell division cycle 2, g1 to S and G2 to M), Gene Registration Number (Genebank) NM_001813 (CENPE, centromere protein E, 312 kDa), Gene Registration Number (Genebank) NM_003579 (RAD54L, RAD54-like (S. cerevisiae)), Gene Registration Number (Genebank) NM_005964 (MYH10, Myosin, heavy chain 10, non-muscle), gene registration number (Genebank) NM_006306 (SMC1A, structural maintenance of chromosomes 1A), gene registration number (Genebank) NM_013257 (SGK3, serum / glucocorticoid regulated kinase family, Member 3), gene registration number ( Genebank) NM_014616 (ATP11B, aTPase, class VI, Type 11B), Gene Registration Number (Genebank) NM_015512 (DNAH1, dynein, axonemal, heavy chain 1), Gene Registration Number (Genebank) NM_016350 (NIN, ninein (GSK3B interacting protein) Genebank NM_018183 (SBNO1, strawberry notch homolog 1 (Drosophila)), Genebank NM_020159 (SMARCAD1, sWI / SNF-related, Matrix-associated actin-dependent regulator of chromatin, subfamily a, containing DEAD / H box 1), Gene Accession Number (Genebank) NM_024320 (ATAD4 , aTPase family, aAA domain containing 4), Genebank NM_024594 (PANK3, pantothenate kinase 3), Genebank NM_033151 (ABCC11, aTP-binding cassette, sub-family C (CFTR / MRP), Member 11), Gene Registration Number (Genebank) NM_182802 (MCM8, Minichromosome maintenance complex component 8), Gene Registration Number (Genebank) NM_207578 (PRKACB, protein kinase, cAMP-dependent, catalytic, Beta), Gene Registration Number (Genebank) NR_002451 (ABCA11, aTP-binding cassette, sub-family A (ABC1), Member 11 (pseudogene)), gene registration number (Genebank) AF042838 (MAP3K1, Mitogen-activated protein kinase kinase kinase 1), gene registration number (Genebank) AL117400 (PASK, pAS domain containing serine / threonine kinase), gene registration number (Genebank) NM_000221 (KHK, ketohexokinase (fructokinase)), gene registration number (Genebank) NM_001005735 (CHEK2, cHK2 checkpoint homolog (S. pombe), Genebank NM_001626 (AKT2, v-akt murine thymoma viral oncogene homolog 2), Genebank NM_001826 (CKS1B, cDC28 protein kinase regulatory subunit 1B), Genebank NM_002758 (MAP2K6, Mitogen-activated protein kinase kinase 6), gene registration number (Genebank) NM_005400 (PRKCE, protein kinase C, epsilon), gene registration number (Genebank) NM_006716 (DBF4, dBF4 homolog (S. cerevisiae)), gene registration Genebank NM_014215 (INSRR, insulin receptor-related receptor), Genebank NM_023110 (FGFR1, fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, pfeiffer syndrome), Genebank NM_032246 (RKHD3, Ring finger and KH domain containing 3), Gene Registration Number (Genebank) NM_052987 (CDK10, cyclin-dependent kinase (CDC2-like) 10), Gene Registration Number (Genebank) NM_001005526 (SF3B1, splicing factor 3b, subunit 1,155 kDa), Genebank NM_002138 (HNRPD) , heterogeneous nuclear ribonucleoprotein D (AU-rich element RNA binding protein 1,37kDa), gene registration number (Genebank) NM_003400 (XPO1, exportin 1 (CRM1 homolog, Yeast)), gene registration number (Genebank) NM_004814 (WDR57, WD repeat domain 57 (U5 snRNP specific), Genebank NM_005033 (EXOSC9, exosome component 9), Genebank NM_006527 (SLBP, stem-loop (histone) binding protein), Genebank (Genebank) ) NM_006638 (RPP40, Ribonuclease P 40kDa subunit), gene registration number (Genebank) NM_006805 (HNRPA0, heterogeneous nuclear ribonucleoprotein A0), gene registration number (Genebank) NM_014953 (DIS3, dIS3 mitotic control homolog (S. cerevisiae)), gene registration number (Genebank) NM_032361 (THOC3, THO complex 3), gene registration number (Genebank) NM_152292 (RG9MTD2, RNA (guanine-9-) methyltransferase domain containing 2), gene registration number (Genebank) AF090937 ( SORBS2, sorbin and SH3 domain containing 2), Genebank NM_000583 (GC, group-specific component (vitamin D binding protein)), Genebank NM_001001290 (SLC2A9, solute carrier family 2 (facilitated glucose transporter) ), Member 9), Genebank NM_001045 (SLC6A4, solute carrier family 6 (neurotransmitter transporter, serotonin, Member 4), Genebank NM_003366 (UQCRC2, ubiquinol-cytochrome c reductase core protein II), Genebank NM_004896 (VPS26A, vacuolar protein sorting 26 homolog A (S.pombe)), Genebank number (Genebank) NM_006028 (HTR3B, 5-hydroxytryptamine (serotonin) receptor 3B), Genebank number NM_006359 (SLC9A6, solute carrier family 9 (s odium / hydrogen exchanger), Member 6), Genebank NM_006416 (SLC35A1, solute carrier family 35 (CMP-sialic acid transporter), Member A1), Genebank NM_006544 (EXOC5, exocyst complex component 5 ), Gene registration number (Genebank) NM_014229 (SLC6A11, solute carrier family 6 (neurotransmitter transporter, gABA), Member 11), gene registration number (Genebank) NM_016057 (COPZ1, coatomer protein complex, subunit zeta 1), gene registration number ( Genebank) NM_016320 (NUP98, nucleoporin 98kDa), Genebank Number (Genebank) NM_018155 (SLC25A36, solute carrier family 25, Member 36), Genebank Number (Genebank) NM_175623 (RAB3IP, RAB3A interacting protein (rabin3), Gene Registration Number (Genebank) AF256215 (ARNTL2, aryl hydrocarbon receptor nuclear translocator-like 2), gene accession number (Genebank) BC041387 (MCTP2, Multiple C2 domains, Transmembrane 2), gene accession number (Genebank) NM_000506 (F2, coagulation factor II (thrombin) )), Gene Registration Number (Genebank) NM_000820 (GAS6, growth arrest-specific 6), Gene Registration Number (Genebank) NM_002317 (LOX, Lysyl oxidase), Gene Registration Number (Genebank) NM_002834 (PTPN11, protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome) 1)), Gene Registration Number (Genebank) NM_003546 (HIST1H4L, histone cluster 1, h4l), Gene Registration Number (Genebank) NM_004311 (ARL3, aDP-ribosylation factor-like 3), Gene Registration Number (Genebank) NM_006203 (PDE4D, phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, drosophila), genebank NM_012096 (APPL1, adapter protein, phosphotyrosine interaction, pH domain and leucine zipper containing 1), genebank NM_012309 (SHANK2) , sH3 and multiple ankyrin repeat domains 2), Genebank NM_012425 (RSU1, Ras suppressor protein 1), Genebank NM_015547 (ACOT11, acyl-CoA thioesterase 11), Genebank NM_016022 (APH1A, anterior pharynx defec tive 1 homolog A (C. elegans)), Genebank NM_024718 (C9orf86, chromosome 9 open reading frame 86), Genebank NM_080651 (THRAP6, Thyroid hormone receptor associated protein 6), Genebank NM_181523 (PIK3R1, phosphoinositide-3-kinase, Regulatory subunit 1 (p85 alpha)), gene accession number (Genebank) NM_194455 (KRIT1, kRIT1, ankyrin repeat containing), gene accession number (Genebank) NM_002089 (CXCL2, chemokine (CXC motif) ligand 2) , Genebank (Genebank) NM_003810 (TNFSF10, Tumor necrosis factor (ligand) superfamily, Member 10), Genebank (Genebank) NM_003811 (TNFSF9, Tumor necrosis factor (ligand) superfamily, Member 9), Gene accession number (Genebank) ) NM_031479 (INHBE, inhibin, Beta E), Genebank NM_017915 (C12orf48, chromosome 12 open reading frame 48), Gene Registration Number (Genebank) BC021267 (KLHL14, kelch-like 14 (Drosophila)) Claim 1 DNA microarray chip for confirming the exposure to the indeno (1,2,3-c, d) pyrene in which the oligonucleotide containing the whole or part of the biomarker gene sequence or its complementary strand molecules are integrated. 1) separating RNA from cells obtained in the subject and untreated human cells as controls; 2) synthesizing RNA of the experimental group and the control group of step 1) with cDNA and labeling the fluorescent substance of each of the experimental group and the control group; 3) hybridizing cDNA labeled with different fluorescent materials of step 2) with DNA microarray chip of claim 4; 4) analyzing the reacted DNA microarray chip of step 3); And 5) indeno (1,2,3-c, d) pyroene exposure is determined by comparing the expression level of the biomarker of the present invention in the analyzed data of step 4) with the control group 1,2,3-c, d) Method for confirming exposure to pyrene. The method according to claim 5, wherein the cells of step 1) are cells derived from human tissue or blood, wherein the cells are exposed to indeno (1,2,3-c, d) pyrene. The method of claim 5, wherein the fluorescent material of step 2) is selected from the group consisting of Cy3, Cy5, poly L-lysine-fluorescein isothiocyanate (FITC), rhodamine-B-isothiocyanate (RITC) and rhodamine (rhodamine) Method for confirming the exposure to indeno (1,2,3-c, d) pyrene, characterized in that. The kit for confirming exposure to indeno (1,2,3-c, d) pyrene, characterized in that it comprises a DNA microarray chip of claim 4. Claim 1 kit for confirming the exposure to indeno (1,2,3-c, d) pyrene comprising a primer pair of 10 to 100 bp length that can specifically amplify the biomarker of claim 1.

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