BIOLOGICAL EFFECTS OF IONIZING RADIATION

EN. MOHD FAHMI B MOHD YUSOF

SCHOOL OF HEALTH SCIENCES UNIVERSITI SAINS MALAYSIA

CONTENTS
Radiation injury mechanism
Direct action Indirect action

Factors modifying biological effect of ionizing radiation Biological effect of ionizing radiation Somatic effect
Deterministic effect Stochastic effect

Outcome of The Class

In the end of the class, you should be able to: 1. Understand water as the main basis for biological effect by ionizing radiation 2. Describe the direct an indirect action in radiation injury mechanism 3. Explain the factors that modify the radiation effects 4. Understand and explain the stochastic and deterministic effect of ionizing radiation 5. Explain the deterministic effect of acute exposure to ionizing radiation 6. Explain the non-fatal deterministic effect of acute exposure to ionizing radiation. 7. Explain the stochastic effect of ionizing radiation

HISTORY IN BIOLOGICAL EFFECT

Henri Becquerel erythema (radium in pocket) Marie Curie died of blood cancer (leukemia) Dial workers mouth cancer Hiroshima/Nagasaki - Leukemia

Early Observation of Effects of Ionizing Radiation

1895 X-ray discovered by Wilhelm C. Rontgen 1896 First skin burn reported 1896 First x-ray use for cancer treatment 1896 Becquerel reported the discovery of radioactivity 1897 First case of skin damage reported 1902 First report of x-ray induced cancer 1903 Mice experiments demonstrate radiation induced leukemia and sterility 1911 First report of leukemia in human and lung cancer from occupational exposure 1911 94 cases of tumor reported in Germany with 50 of them are radiologists

Radiation Injury Mechanism

Radiation effects occur at the physiochemical levels in cells, organs and the whole body Water 80% of the content of a biological system
Interaction with water is the main basis for biological effects Radiation interaction with water causes complex chemical changes

Radiation Injury Mechanism

Radiations direct and indirect interaction through various chemical species
Most interactions are indirect interaction through hydrogen and hydroxyl (OH-) radicals on DNA molecule DNA has critical and strategic role in cells function. Radiation alters cells characteristics, function and may cause cell death

Radiation Injury Mechanism

Not all exposure will cause cell death
Low doses may cause damage that could be rectified. The damaged molecules might be replaced or be repaired by the cell after some time, and the cell may then perform its normal function. However, not all damages could be repaired.

Radiation Injury Mechanism Action Mechanism

Direct action:
Interaction of ionizing radiation with atoms of water molecules producing ion pairs. The electron produced from the interaction attacked with the DNA strands, breaking the DNA molecules.

Radiation Injury Mechanism

Indirect action:
The ionizing radiation interact with water molecules producing ion pairs. The electron resulted from the interaction interact with another water molecules Water molecules break into free radical (OH-) and hydrogen ion (H+) The free radical is very reactive as it interact and breaks the DNA structure

Radiation Injury Mechanism

Action Mechanism

Direct action H+ OHIndirect action

BASIC CONCEPT OF RADIOBIOLOGY

Interaction is a probabilistic event (stochastic). Transfer of energy occurs extremely quickly: approximately 10-17s. Thus, radiation protection must be applied before irradiation. There is always a damage to the cells. A consequence could be cancer induction. The damage is not specific. It is similar to other etiologic agents. There are targets in every cell (point where are more probably affected by ionizing radiation).

BASIC CONCEPT OF RADIOBIOLOGY

Time Scale Fractions of Seconds Seconds Minutes
Hours Days Weeks Months

Years Decades Generations

Effects Energy absorption changes in biomolecules (DNA) Biological repair Changes of cell information Cell Death Mutations Organ Clinical germ somatic death changes cell cell leukemia Hereditary or effect cancer

FACTORS THAT MODIFY RADIATION EFFECTS

1. Type of Radiation
Characteristics of alpha, beta, gamma and x-ray, and neutrons will modify radiation effects. A simple way to determine the degree of hazard by ionizing radiations are using the radiation weighting factor WR Radiation quality is also stated by RBE and LET values, type and energy of radiation. Radiation with higher RBE and LET values will cause more damages. Radiation with higher penetrative power is better able to cause damage to organs deeper inside the body.

FACTORS THAT MODIFY RADIATION EFFECTS

TYPES AND ENERGY RANGE OF RADIATION
Photon, all energies Electron, all energies Neutron, energy < 10keV 10 keV to 100keV >100keV to 2MeV > 2MeV to 20MeV >20MeV

WR
1 1 5 10 20 10 5

Proton, other than recoil proton, energies >2MeV

Alpha particle, fissions, heavy nucleus

5
20

FACTORS THAT MODIFY RADIATION EFFECTS 2. Total Dose and Dose Rate
The bigger is the total dose, the more severe is the effect Effects of dose rate: 10Sv, whole body, one shot, 100% death 10Sv, in two shots, 5Sv and 5Sv, within 48 hours time interval: Probability of death < 100% 10Sv, total dose, gradually over period of 50 years: No acute effect.

FACTORS THAT MODIFY RADIATION EFFECTS cont..

3. Part of The Body Exposed
Different parts of the body have different importance and level of sensitivity towards radiation. Location of the radiation source: Eg. Alpha radiation from outside a body will not cause any damage, but alpha source inside a body is extremely dangerous. Non-uniform distribution of radionuclide inside a body Some will concentrate in a particular organ in a body and cause more damage. Eg. Iodine to thyroid glands and radium to bones.

FACTORS THAT MODIFY RADIATION EFFECTS cont..

TISSUE OR ORGAN W

Gonad

0.20

Bone marrow
Lower large intestine Lung Stomach

0.12
0.12 0.12 0.12

Bladder
Breast Liver Esophagus

0.05
0.05 0.05 0.05

Thyroid
Bone surface Skin Brain, kidney, muscle, pancreas, small intestine, thymus, upper large intestine, uterus.

0.05
0.01 0.01 0.05

FACTORS THAT MODIFY RADIATION EFFECTS cont..

4. Biological and Chemical Factors
Age, sex, state of health and state of endocrinal system may modify radiation effects Type of food consumed, oxygen concentration and presence of various chemicals may modify biological effects of radiation.

FACTORS THAT MODIFY RADIATION EFFECTS cont..

5. Radiological Sensitivities of Cells
Different types of cells have different levels of sensitivities towards radiation Generally, radiological sensitivity of cell is directly proportional to its divisional activities and inversely proportional to its differentiation.

Spermatogonium and erythroblast are actively dividing cells - most radiosensitive cells Muscle and nerve cells are highly differentiate and are not actively dividing - the most resistant to radiation effects. Lymphocyte is an example of an exception. It is highly sensitive to radiation even though it is highly differentiate and do not divide.

Biological Effect of Ionizing Radiation

Deterministic effect

SOMATIC Stochastic effect

Biological effect
Dominant GENETIC Recessive

Biological Effect of Ionizing Radiation

Somatic effects radiation damage appears in the exposed individual which can be: Deterministic effect (early effect/nonstochastic effect) Stochastic effect (late/long term effect)

Hereditary / genetic effect manifest in the offsprings of the exposed person as a result of radiation damage to the reproductive organs or the gonads

Biological Effect of Ionizing Radiation

Deterministic effect:
Existence of dose threshold where below this dose, the effect is not observable. Effect severity increase with increasing dose. Eg. Lens opacities, skin lesions, etc.

Stochastic effect:
No threshold Probability of the effect increase with dose. Severity is weighted by factor G. for fatal cancer and extreme genetic effects, G=1, for non-fatal cancers, G<1. Eg. Cancer, genetic mutation.

Deterministic Effect
There exist threshold for deterministic effects. Clinically observable loss of tissue function Will always be seen above some treshold dose which damages a sufficient number of cells. Examples: cataract, cell damage, bone marrow damage, tissue damage. Severity of its effect is proportional to the dose received.

Whole body Response for Deterministic Effect

Acute irradiation syndrome
1-10Gy Survival time 10-50Gy

>50Gy

Steps: 1. Prodromic 2. Latency 3. Manifestation

Dose

Deterministic Effect
Lethal Dose 50/30 It is an expression of the percentage lethal dose as a function of time. It means Dose which could cause death for 50% of the population in 30 days. Its value is about 2-3Gy for humans or whole body irradiation.

Deterministic Effect
An acute exposure of ionizing radiation may cause: 1. Prodromal syndrome 2. Bone marrow syndrome 3. Gastrointestinal syndrome 4. Central nervous system syndrome

Deterministic Effect
1. Prodromal Syndrome
Whole body irradiation to 1-10Gy of radiation Early symptoms of radiation syndrome are nausea, vomiting, diarrhea, loss of appetite and headache. Its severity is dependent on the magnitude of the radiation dose received. Existence of latent period, the period where the effects do not appear sometimes.

Deterministic Effect
2. Bone Marrow / Haematopoeitic Syndrome
Dose threshold level for effect to be felt is 1Sv. Probability of death begins with whole body dose of 2Sv. All blood cell originate from the stem cells. Stem cells are very sensitive to radiation. This will reduce the number of blood cells in the blood system. Symptoms of the syndrome: Nausea, vomiting, paleness The symptoms may temporarily disappear during the latent period. The latent period will be followed by feeling of lethargy, tiredness, loss of appetite and fever.

Deterministic Effect
Effect of reduction of blood cells: Anemia, hypoxia. Collapse of body defense system and it becomes less able to defend itself against bacterial attacks. Failure to clot blood causing internal bleeding Survival or death will be determined within 30 days.

Deterministic Effect
3. Gastrointestinal Syndrome Threshold level of 4Sv. It is caused by irradiation to the gastrointestinal system. Its effect is felt almost immediately. It causes the following symptoms; All symptoms of prodromal syndrome Severe gastrointestinal pain The syndrome causes damage to the gastrointestinal system that is: Destruction of cript cells. This causes failure to replace mucosa cells that is covering and protecting the viluses. This failure exposes gstrointestinal system to bacterial infections and blood poisoning. Death within a week.

Deterministic Effect
4. Central Nervous System Syndrome
Threshold level >50Sv , exposure to central nervous system. Death due to damage to central nervous system. Victim will suffer motor incoordination, hyper-excitation and coma Death within 2-3 days.

Deterministic Effect
Non-Fatal Acute Effects 1. Effects to skin
3-8Sv, cause effect similar to sunburn 10Sv, causes effect which is equivalent to second-degree burn and will leave permanent scars 50Sv, cause severe injury

Deterministic Effect
2. Effect to hair 3-4Sv, causes hair loss, but will regrow as white and coarse hairs 7Sv, cause permanent hair loss 1.5-2Sv, cause temporary infertility for 1-3 years. 2.5-6Sv, cause permanent infertility.

3.

Effects to fetus Exposure to pre attachment embryo will cause abortion Exposure during organ formation stage will cause defects to the organ affected.

Deterministic Effect
4. Effects to gonad
Male: 0.1Sv, cause very low sperm count 2.5Sv, causes infertility for 2-3 years 3.5-6Sv, cause permanent infertility Female: Similar effect for male Exposure during growth stage, fetus is 1.5 to 2 times more sensitive to radiation compared to adults. It increases probability of cancer incidence.

Deterministic Effect
5. Effects to eye lens
0.2 0.5Sv, causes opacification of eye lens. 2 10Sv, causes blindness through cataract The above affects appear few months to a few years after exposure.

Stochastic Effects
The occurrence of stochastic effect is probabilistic in nature. Eg, cancer. Probability of occurrence is proportional to the dose received. It is almost impossible to prove that a particular cancer has been cause by ionizing radiation. Similar cancer could also be caused by various chemicals, hormones, viruses, UV radiation etc. Threshold level does not exist for stochastic effect. The physical effects in on the receiver of radiation dose himself (somatic). The effect does not appear immediately The effect may be delayed for a long time, that is a few years to decades. It is also called delayed effect.

TISSUE RISK FACTOR

The quotient of increase in probability of a stochastic effect and the received dose. It is measured in Sv-1 or mSv-1.
% effect

probability dose Dose Risk Factor = probability dose

TISSUE RISK FACTOR

Example: a risk factor of 0.005 Sv-1 for bone marrow (lifetime mortality in a population of all ages from specific fatal cancer after exposure to low doses) means that if 1000 people would receive 1Sv to the bone marrow, 5 will die from a cancer induced by radiation.

RISK OF GENETIC EFFECT

ICRP gave the value of 0.6 x 10-2 Sv-1 per year for the risk of genetic effect due to exposure to radiation.

Estimates of Probability of Occurrence For Various Types of Cancer Due to Exposure to Radiation
Cancer Type
Bone marrow Bone surface Lung Thyroid Breast Colon Stomach Bladder Esophagus Liver Skin Gonad Other TOTAL

Probability of Fatal Cancer, 10-4 Sv-1

50 5 85 8 20 85 110 30 30 15 2 10 50 500 x 10-4 Sv-1

Estimates of Loss of Life-Time Due to Various Activities and Causes

Activity / Cause
Smoking Overweight by 30% Stroke Car accidents Accidents at home Average occupational accidents Occupations involving radiation Pedestrian accidents The safest occupation Medical x-ray Drinking coffee

Loss of Life-Time (days)

2,250 1,300 520 207 95 74 40 37 8 6 6

1 Chest x-ray Equivalent to 3 days of annual background radiation Risk of cancer death 1 in a million Though the risk is very small, but many people still fear radiation despite its diagnostic value.

1 Mammography Equivalent to 0.1 to 0.2 rad dose per picture 1 mammography equivalent to flying in commercial jet from New York to California