Abstract
The aim of this study was to evaluate DNA damage and the capacity for DNA repair in children exposed to arsenic and lead. During 2006, we studied a total of 85 healthy children (aged 4–11 years) who were residents of Villa de la Paz (community A), Matehuala (community B), and Soledad de Graciano Sanchez (community C) in San Luis Potosi, Mexico. The quantification of arsenic in urine (AsU) and lead in blood (PbB) was performed by atomic absorption spectrophotometry. The alkaline comet assay was used to evaluate DNA damage and DNA repair. The highest levels of AsU and PbB in children were found in community A (44.5 μg/g creatinine for arsenic and 11.4 μg/dL for lead), followed by community B (16.8 μg/g creatinine for arsenic and 7.3 μg/dL for lead) and finally by children living in community C (12.8 μg/g creatinine for arsenic and 5.3 μg/dL for lead). When DNA damage was assessed, children living in community A had the highest DNA damage. Analysis of these same cells 1 h after a challenge with H2O2 10 μM showed a dramatic increase in DNA damage in the cells of children living in community B and community C, but not in the cells of children living in community A. Moreover, significantly higher levels of DNA damage were observed 3 h after the challenge ended (repair period) in cells from individuals living in community A. Our results show that children exposed to metals might be more susceptible to DNA alterations.
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Rodríguez VM, Dufour L, Carrizales L, Díaz-Barriga F, Jimenez-Capdeville ME (1998) Effects of oral exposure to a mining waste on in vivo dopamine release from rat striatum. Environ Health Perspect 106:487–491
Razo I, Carrizales L, Castro J, Díaz-Barriga F, Monroy M (2004) Arsenic and heavy metal pollution of soil, water, and sediments in a semiarid climate mining area in Mexico. Water Air Soil Pollut 152:129–152
Yáñez L, Garcıía-Nieto E, Rojas E, Carrizales L, Mejıía J, Calderón J, Razo I, Dıíaz-Barriga F (2003) DNA damage in blood cells from children exposed to arsenic and lead in a mining area. Environ Res 93:231–40
IARC (International Agency for Research on Cancer) (2004) Arsenic in drinking-water. IARC Monogr Eval Carcinog Risks Hum 84:39–267
ATSDR (2008) Toxicological profile for arsenic. Agency for Toxic Substances and Diseases Registry, Atlanta
Ruiz-Ramos R, Lopez-Carrillo L, Rios-Perez AD, De Vizcaya-Ruiz A, Cebrian ME (2008) Sodium arsenite induces ROS generation, DNA oxidative damage, HO-1 and c-Myc proteins, NF-kappaB activation and cell proliferation in human breast cancer MCF-7 cells. Mutat Res 674:109–115
Kojima C, Ramirez DC, Tokar EJ, Himeno S, Drobna Z, Styblo M, Mason RP, Waalkes MP (2009) Requirement of arsenic biomethylation for oxidative DNA damage. J Natl Cancer Inst 101:1670–1681
Huang C, Qingdong K, Costa M, Shi X (2004) Molecular mechanisms of arsenic carcinogenesis. Mol Cell Biochem 255:57–66
Asmuss M, Mullenders LH, Eker A, Hartwig A (2000) Differential effects of toxic metal compounds on the activities of Fpg and XPA, two zinc finger proteins involved in DNA repair. Carcinogenesis 21:2097–2104
Hartwig A, Blessing H, Schwerdtle T, Walter I (2003) Modulation of DNA repair processes by arsenic and selenium compounds. Toxicology 193:161–169
Hartwig A, Pelzer A, Asmuss M, Bürkle A (2003) Very low concentrations of arsenite suppress poly(ADP-ribosyl)ation in mammalian cells. Int J Cancer 104:1–6
Nollen M, Ebert F, Moser J, Mullenders LH, Hartwig A, Schwerdtle T (2009) Impact of arsenic on nucleotide excision repair: XPC function, protein level, and gene expression. Mol Nutr Food Res 53:572–582
Schwerdtle T, Walter I, Hartwig A (2003) Arsenite and its biomethylated metabolites interfere with the formation and repair of stable BPDE-induced DNA adducts in human cells and impair XPAzf and Fpg. DNA Repair (Amst) 2:1449–1463
Jensen TJ, Novak P, Eblin KE, Gandolfi AJ, Futscher BW (2008) Epigenetic remodeling during arsenical-induced malignant transformation. Carcinogenesis 29:1500–1508
Zhou X, Sun H, Ellen TP, Chen H, Costa M (2008) Arsenite alters global histone H3 methylation. Carcinogenesis 29:1831–1836
Baccarelli A, Bollati V (2009) Epigenetics and environmental chemicals. Curr Opin Pediatr 21:243–251
Singh KP, DuMond JW Jr (2007) Genetic and epigenetic changes induced by chronic low dose exposure to arsenic of mouse testicular Leyding cells. Int J Oncol 30:253–260
Jensen TJ, Wonzniak RJ, Eblin KE, Wnek SM, Gandolfi AJ, Futscher BW (2009) Epigenetic mediated transcriptional activation of WNT5A participates in arsenical-associated malignant transformation. Toxicol Appl Pharmacol 235:39–46
Andrew AS, Burgess JL, Meza MM, Demidenko E, Waugh MG, Hamilton JW, Karagas MR (2006) Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic. Environ Health Perspect 11:1193–1198
Devi KD, Banu BS, Grover P, Jamil K (2000) Genotoxic effect of lead nitrate on mice using SCGE (comet assay). Toxicology 145:195–201
Valverde M, Fortoul IT, Díaz-Barriga F, Mejía J, Rojas CE (2002) Genotoxicity induced in CD-1 mice by inhaled lead: differential organ response. Mutagenesis 17:55–61
Ye XB, Fu H, Zhu JL, Ni WM, Lu YW, Kuang XY, Yang SL, Shu BX (1999) A study on oxidative stress in lead-exposed workers. J Toxicol Environ Health A 57:161–172
Gastaldo J, Viau M, Bencokova Z, Joubert A, Charvet AM, Balosso J, Foray N (2007) Lead contamination results in late and slowly repairable DNA double-strand breaks and impacts upon the ATM-dependent signaling pathways. Toxicol Lett 173:201–214
Karakaya AE, Ozcagli E, Ertas N, Sardas S (2005) Assessment of abnormal DNA repair responses and genotoxic effects in lead exposed workers. Am J Ind Med 47:358–363
Link B, Gabrio T, Zoellner I, Piechotowski I, Paepke O, Herrmann T, Felder-Kennel A, Maisner V, Schick KH, Schrimpf M, Schwenk M, Wuthe J (2005) Biomonitoring of persistent organochlorine pesticides, PCDD/PCDFs and dioxin-like PCBs in blood of children from South West Germany (Baden—Wuerttemberg) from 1993 to 2003. Chemosphere 58:1185–1201
Guzelian PS, Henry CJ, Olin SS (eds) (1992) Similarities and differences between children and adults: implications for risk assessment. ILSI, Washington, DC
Bearer CF (1995) Environmental health hazards: how children are different from adults. Future Child Crit Issues Child Youths 5:11–26
Carlson JE (1998) Children’s environmental health: research, practice, prevention and policy. Environ Health Perspect 106:785–862
Galson SK, Carroquino MJ, Landrigan PJ (1998) Preventable cause of cancer in children. Environ Health Perspect 106:865–925
Aprea C, Strambi M, Novelli MT, Bozzi N (2000) Biologic monitoring of exposure to organophosphorus pesticides in 195 Italian children. Environ Health Perspect 108:521–525
Needham LL, Sexton K (2000) Assessing children’s exposure to hazardous environmental chemicals: an overview of selected research challenges and complexities. J Expo Anal Environ Epidemiol 10:611–629
Adgate JL, Sexton K. Children’s exposure to pesticides in residential settings. In: Krieger, R. (ed) (2001) Handbook of pesticide toxicology. Academic, San Diego, CA. pp. 887–904.
Brent R, Tanski S, Weitzman M (2004) A pediatric perspective on the unique vulnerability and resilience of the embryo and the child to environmental toxicants: the importance of rigorous research concerning age and agent. Pediatrics 113:935–944
IPCS (2006) Principles for evaluating health risk in children associated with exposure to chemical. Environmental Health Criteria 237.
Cox DH (1980) Arsine evolution—electrothermal atomic absorption method for the determination of nanogram levels of total arsenic in urine and water. J Anal Toxicol 4:207–211
Subramanian KS (1987) Determination of lead in blood: comparison of two GFAAS methods. At Spectros 8:7–14
Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191
Collins A (2004) The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol 26:249–261
Jasso-Pineda Y, Espinosa-Reyes G, González-Mille D, Razo-Soto I, Carrizales L, Torres-Dosal A, Mejia-Saavedra J, Monroy M, Ize AI, Yarto M, Díaz-Barriga F (2007) An integrated health risk assessment approach to the study of mining sites contaminated with arsenic and lead. Integr Environ Assess Manag 3:344–350
Méndez-Gómez J, García-Vargas GG, López-Carrillo L, Calderón-Aranda ES, Gómez A, Vera E, Valverde M, Cebrián M, Rojas E (2008) Genotoxic effects of environmental exposure to arsenic and lead on children in region Lagunera, México. Ann NY Acad Sci 1140:358–367
Ding W, Hudson LG, Liu KJ (2005) Inorganic arsenic compounds cause oxidative damage to DNA and protein by inducing ROS and RNS generation in human keratinocytes. Mol Cell Biochem 279:105–112
Chakraborty T, Das U, Poddar S, Sengupta B, De M (2006) Micronuclei and chromosomal aberrations as biomarkers: a study in an arsenic exposed population in West Bengal, India. Bull Environ Contam Toxicol 76:970–976
Chakraborty T, De M (2009) Clastogenic effects of inorganic arsenic salts on human chromosomes in vitro. Drug Chem Toxicol 32:169–173
Vuyyuri SB, Ishaq M, Kuppala D, Grover P, Ahuja YR (2006) Evaluation of micronucleus frequencies and DNA damage in glass workers exposed to arsenic. Environ Mol Mutagen 47:562–570
Mahata J, Chaki M, Ghosh P, Das LK, Baidya K, Ray K, Natarajan AT, Giri AK (2004) Chromosomal aberrations in arsenic-exposed human populations: a review with special reference to a comprehensive study in West Bengal, India. Cytogenet Genome Res 104:359–364
ATSDR (2008) Toxicological profile for PAHs. Agency for Toxic Substances and Diseases Registry, Atlanta, GA
Evans CD, LaDow K, Schumann BL, Savage RE Jr, Caruso J, Vonderheide A, Succop P, Talaska G (2004) Effect of arsenic on benzo[a]pyrene DNA adduct levels in mouse skin and lung. Carcinogenesis 25:493–497
Drobna Z, Naranmandura H, Kubachka KM, Edwards BC, Herbin-Davis K, Styblo M, Le XC, Creed JT, Maeda N, Hughes MF, Thomas DJ (2009) Disruption of the arsenic (+3 oxidation state) methyltransferase gene in the mouse alters the phenotype for methylation of arsenic and affects distribution and retention of orally administered arsenate. Chem Res Toxicol 22:1713–1720
Petrick JS, Jagadish B, Mash EA, Aposhian HV (2001) Monomethylarsonous acid (MMAIII) and arsenite: LD50 in hamsters and in vitro inhibition of pyruvate dehydrogenase. Chem Res Toxicol 14:651–656
Styblo M, Drobna Z, Jaspers I, Lin S, Thomas DJ (2002) The role of biomethylation in toxicity and carcinogenicity of arsenic: a research update. Environ Health Perspect 110:767–771
Colognato R, Coppede F, Ponti J, Sabbioni E, Migliore L (2007) Genotoxicity induced by arsenic compounds in peripheral human lymphocytes analysed by cytokinesis-block micronucleus assay. Mutagenesis 224:255–261
Sampayo-Reyes A, Hernandez A, El-Yamani N, Lopez-Campos C, Mayet-Machado E, Rincon-Castañeda CB, Limones-Aguilar M, Lopez-Campos JE, Bermudez de Leon M, Gonzalez-Hernandez S, Hinojosa-Garza D, Marcos R (2010) Arsenic induces DNA damage in environmentally exposed Mexican children and adults. Influence of GSTO1 and AS3MT polymorphisms. Tox Sci 117:63–71
ATSDR (2008) Toxicological profile for lead. Agency for Toxic Substances and Diseases Registry, Atlanta, GA
Nordenson I, Beckman G, Beckman L, Nordström S (1978) Occupational and environmental risks in and around a smelter in northern Sweden: IV. Chromosomal aberrations in workers exposed to lead Hereditas 88:263–267
Bauchinger M, Dresp J, Schmid E, Englert N, Krause C (1977) Chromosome analyses of children after ecological lead exposure. Mutat Res 56:75–79
Wu FY, Chang PW, Wu CC, Kuo HW (2002) Correlations of blood lead with DNA-protein cross-links and sister chromatid exchanges in lead workers. Cancer Epidemiol Biomarkers Prev 11:287–290
Duydu Y, Suzen HS, Aydin A, Cander O, Uysal H, Işimer A, Vural N (2001) Correlation between lead exposure indicators and sister chromatid exchange (SCE) frequencies in lymphocytes from inorganic lead exposed workers. Arch Environ Contam Toxicol 41:241–246
Dalprà L, Tibiletti MG, Nocera G, Giulotto P, Auriti L, Carnelli V, Simoni G (1983) SCE analysis in children exposed to lead emission from a smelting plant. Mutat Res 120:249–256
Fracasso ME, Perbellini L, Soldà S, Talamini G, Franceschetti P (2002) Lead induced DNA strand breaks in lymphocytes of exposed workers: role of reactive oxygen species and protein kinase C. Mutat Res 515:159–169
Danadevi K, Rozati R, Saleha Banu B, Hanumanth Rao P, Grover P (2003) DNA damage in workers exposed to lead using comet assay. Toxicology 187:183–193
Beyersmann D, Hartwig A (2008) Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms. Arch Toxicol 82:493–512
Hartwig A, Groblinghoff UD, Beyersmann D, Natarajan AT, Filon R, Mullenders LH (1997) Interaction of arsenic(III) with nucleotide excision repair in UV-irradiated human fibroblasts. Carcinogenesis 18:399–405
Lee-Chen SF, Yu CT, Jan KY (1992) Effect of arsenite on the DNA repair of UV-irradiated Chinese hamster ovary cells. Mutagenesis 7:51–55
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This work was supported by a grant from the Consejo Nacional de Ciencia y Tecnología, Mexico, CONACYT-SEP 24024.
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Jasso-Pineda, Y., Díaz-Barriga, F., Calderón, J. et al. DNA Damage and Decreased DNA Repair in Peripheral Blood Mononuclear Cells in Individuals Exposed to Arsenic and Lead in a Mining Site. Biol Trace Elem Res 146, 141–149 (2012). https://doi.org/10.1007/s12011-011-9237-0
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DOI: https://doi.org/10.1007/s12011-011-9237-0