Biological Effects of Radiation KJ350 deborah.oughton@nmbu.no 2111 2005
Radiation Biology Interaction of radiation with biological material Doses (Gy, Sv) and effects Scientific Controversy Radiation Protection Recommendations of the International Commission of Radiological Protection (ICRP) 2
Definitions Radioactivity: a phenomenon linked to the nucleus of an atom Radionuclides: unstable atoms, wherein the nuclear composition changes over time, accompanied by the emission of radiation to reach a more stable state Radiation: emission or transfer of energy as particles, electromagnetic waves, etc. Isotopes: chemical elements with different atomic weights (number of neutons). Can be stable or unstable 3 X-rays are ionising radiation, but NOT radioactivity!
alpha gamma beta Neutrons (fission only) X-rays Nuclide: A X N Z X-Element Z Proton number N Neutron number A Mass number Emission of radiation as a result of radioactive decay 4 MINA 200 Radioaktiv kilder (deborah Oughton, IPM)
Ionizing radiation α - radiation: β - radiation: MINA 200 Radioaktiv kilder (Deborah Oughton, IPM) γ - radiation: Particle types 5
Radiation interaction with biological material Ionising radiation Damage repaired successfully Damage repaired unsuccessfully Cell mutation Cell death DNA Damage Somatic cell Germ line cell DETERMINISTIC STOCHASTIC EFFECT tissue reaction EFFECT effects
Excitation free radical induction H 2 O H 2 O * H 2 O *. H +. OH H 2 O * H 2 O Damage to membranes, tissues, enzymes, proteins, DNA/RNA Reactive Oxygen Species (ROS) Oxidative Stress Low doses : Indirect Effects Dominate 7
Stochastic and deterministic effects Stochastic Dose (Gy) Dose (mgy) 8 Deterministic
Biological endpoints Cytogenetic effects (DNA damage, chromosome aberrations) Cancer Immunological effects?? Cardiovascular effects?? Underlying mechanisms uncertain Cell death Radiation burns Reproductive effects (fertility, fecundity, still births, mutations) Organ failure - death 9
Possible Dose-Response Relationships at low doses (msv) 10
Underlying Mechanisms and Dose Response Cancer and Tissue Effects 11
Mutation to Cancer Many Stages between mutation and effect Many factors can impact on the outcome : Dose characteristics Diet Genetic susceptability Other biological stressors Dose rate Radiation type (biological effectiveness) External/internal irradiation Organ irradiated 12
DNA Repair DNA Damage 13
DNA Damage Direct and Indirect Effects Human body contains 10 14 cells Chromosomes only ~1% of cell volume and only 10% of that contains a genetic message Radiation interaction on cell nucleus via ionisation, excitation, free radical production in water Specific damage: single strand breaks, double strand breaks, chromosome aberrations, base-pair alterations (adducts, bond breaks) Radiation DNA effects similar to other genotoxins, but differ in that localised clusters of effects can occur 14
High and Low-LET (Linear Energy Transfer) Radiation β α 15
Damage in a single-cell-nucleus (per radiation track) Average number of induced breaks Radiation Average nr of ionisations DNA single strand break DNA double strand break γ-ray 70 1 0.04 (low LET) (1-1500) (0-20) (0-few) α-particles 23000 200 35 (High LET) (1-100000) (0-400) (0-100) 1 mgy average 1 track per cell
Summary Mechanisms and Dose Characteristics High Doses Direct damage to DNA Many double strand breaks Low doses; Low LET Indirect effects (via ROS) Single strand breaks predominate Low doses; High LET (alpha emitters) Indirect effects Double strand breaks more frequent 17
Biology : Internal and External Exposure Internal: ingestion, inhalation Alpha emitters, eg. Rn-222 + daughters, Puisotopes Internal/Short-range external Pure beta-emitters, eg. C-14, S-35, P-32, Sr-90, H-3 External and Internal Gamma-emitters and beta-emitters, e.g. Zn-65, Ca-47, Cs-137 Alexandre Litvinenko Polonium poisoning 18
Biology where in the body? I-131 (beta, gamma) Thyroid (thyroid cancer) Cs-137 (beta, gamma) Muscle (solid tumour cancers) Sr-90 (beta), Pu-isotopes (alpha) Bone seekers (leukaemia) Dose Conversion Factor Tables (Sv/Bq ingested/inhaled radionuclide) Chernobyl Thyroid Victims 19
Individual doses (EPA Japan) Tittel på presentasjon Norwegian University of Life Sciences 20
Cancer risk co-efficients (ICRP, 2011) Risk of detriment = 0.057 per Sv (Detriment = 0.055 cancer + 0.002 hereditary effects for populations*) Approximate overall fatal risk coefficient = 5*10-5 per msv = 5*10-4 per 10mSv Expected 1 mortality for every 1,000 people exposed to 20 msv * 0.041 and 0.001 for adults 21
Where do the risk estimates come from? Epidemiological studies Poplations exposed to radiation doses (Gy) Estimate w T and Risk coefficients Count number of excess organ specific cancers and deaths 22 More in KJM360: Assessing risks to Man and Environment
Epidemiological Studies - Cancer Nagasaki and Hiroshima Test veterans Medical uses Accidents (Chernobyl, Khystym, Mayak workers) Enhanced natural radioactivity Problems: high background cancer rate, extrapolations, animal data, etc. etc. 23
From Bq to Sv: Dose calculations and Risk Estimates 24
Average Sources of Radiation Exposure - Europe Background (natural) Doses = 2-5 msv/yr 25
Absorbed dose (Gy) Energy deposited in a tissue or organ (Joules/kg) due to radiation exposure Unit - the Gray (Gy) Dependent on the energy of radiation and its interaction with the biological material Primarily derived from estimates of linear energy transfer (LET) in water (ev/nm) Old unit the rad (radiation adsorbed dose) 26
Equivalent Dose: Sievert (Sv) H T (Sv) = Σ w R D T,R w R = radiation weighting factor D T,R = adsorbed dose averaged over the tissue or organ, T, due to radiation, R (Gy) Old unit, rem, 1 Sv = 100 rem 27
RBE= Experimental measurement any effect or endpoint w R W R = Committee decision for use in Risk assessment only cancer 28
Effective Dose (Whole Body): Sv E (Sv) = Σ w T H T w T = tissue weighting factor w T = nornmalises for risk of cancer death; depends on organ being irradiated and sensitivity of that organ to fatal cancer See ICRP 103 (www.icrp.org) 29
From Annex A
Weighting factors - Summary Radiation weighting factors, w R Type of Radiation Photons, electrons 1 w R Alpha particles 20 Neutrons 5-20 (Tritium?) Tissue weighting factors, w T Tissue or organ w T Gonads 0.20 Bone marrow 0.12 Colon 0.12 Lung 0.12 Stomach 0.12 Breast, Oesophagus, thyroid, liver 0.05 Skin, bone surface, remainder 0.01
Collective and Committed Dose Collective dose (Dose to a population) mansv (S T ) = sum of whole body dose over individuals Committed dose (Dose over more than one year) sum of H T or E over time 32
Summary Example: Radon in Norway Mean adsorbed lung dose from radon and daughters = 1.2 mgy/year Equivalent dose to lungs (Gy*w R ) = 1.2 x 20 = 24 msv Annual effective dose (Sv*w T ) = 24 * 0.12 = 2.9 msv Collective dose (population*sv) = 5 10 6 * 2.9 10-3 = 14500 mansv Estimated cases of fatal cancer (risk factor * mansv) = 0.05*14500 = 725
Average Sources of Radiation Exposure - Europe Background (natural) Doses = 2-5 msv/yr 34
Scientific Controversy in Radiation Biology - Dose Calculations Dose characteristics Extrapolation from High dose to Low dose Acute or chronic (protracted) doses Radionuclide characteristics α, β, γ emitter (auger emitter, neutron source) Metabolism (bioavailability, uptake and excretion rates, where in body, chemical speciation) 35
Factors influencing dose response (KJM351 and MINA 410 Environmental Radiobiology) DNA repair vs apoptosis Gene and protein expression Different mechanisms at high/low dose: e.g., bystander effect, genomic instability, adaptive response Cell cycle status Oxygen status Radiosensitivity, genetic factors 36
International Commission for Radiological Protection (ICRP): Independent organisation in existence since 1927 Initially provided guidance on medical uses of radiation Provides Recommendations and Advice on Radiological Protection, Emergency Prepardeness and Nuclear safety www.icrp.org 37
ICRP Three Stage Philosophy for Radiological Protection The Principle of Justification: Any decision that alters the radiation exposure situation should do more good than harm. The Principle of Optimisation of Protection: The likelihood of incurring exposure, the number of people exposed, and the magnitude of their individual doses should all be kept as low as reasonably achievable (ALARA), taking into account economic and societal factors. The Principle of Application of Dose Limits: The total dose to any individual from regulated sources in planned exposure situations other than medical exposure of patients should not exceed the appropriate limits specified by the Commission. ICRP 103 (2007) 38
Dose Limits Workers 20 msv per year over a 5 year period (in some countries additional criteria that maximum in one year not exceed 50m Sv) Public 1 msv per year over a 5 year period (all nuclear practice sources) Pregnant workers 1 msv to the foetus after pregnancy has been confirmed Norway Radiation Protection Act 2000 See: www.nrpa.no legislation (regelverk) 39
ALI Annual Limit of Intake Calculation of maximum intake rates (ingestion and inhalation) in Bq Calculation of the maximum levels of intake that can be accepted in food (Council Food Intervention Limits, Codex values FAO) Cs-137 limits in foodstuff: Reindeer 3000 Bq/kg; milk 100 Bq/kg 40
Effects on non-human species: Traditional focus on humans: If man is adequately protected, then other living things are also likely to be sufficiently protected (ICRP, 1977, 1991) Since 2000, emerging consensus that also need to consider the effects of ionising radiation on non-human species (Included in new Recommendations, 2007) Requirement for enormous amount of information on transfer, uptake and effect of ionising radiation (particularly for wild species) 41
Lethal dose from acute, high doses Reproductive effects seen at doses 10-100x lower than lethal effects Figure 3.1 Comparative radiosensitivity of different organisms demonstrated as the acute lethal dose ranges (reproduced from UNSCEAR 1996). 42
Summary Radiation Effects and Radiation Protection Radiation causes damage to biological systems by the deposition of energy in tissues Deterministic effects occur at high doses cell killing Stochastic effects (e.g. cancer and hereditary effects) occur at low doses DNA damage The radiation dose (Gray) provides a measure of the deposition of energy in tissues, and is correlated with a risk of biological damage following exposure to ionising radiation The Sievert gives an estimate of the risk of detriment from cancer mortality and hereditary effects weighted for radiation type and tissue sensitivity Average Natural Background Radiation doses are in the order of 2-5 msv per year, the majority being from radon exposure The ICRP framework for radiation protection is based on the Linear-No- Threshold (LNT) Model and assumes that there is no threshold Annual dose limits are 1 msv for the public and 20 msv for workers. 43