IAEA PGEC Pre-Study Materials Biology and Radiation Effects IAEA International Atomic Energy Agency Table of Contents Topic Slide Living Organisms and Cellular Structure………………... 5 Macromolecules………………………….…………............. 9 The Nucleus …………………………….…………………… 14 The Cell Cycle……………………………………………….. 21 Cellular Damage From Radiation…..……………………. 28 Cell Response to Radiation Damage…………………… 40 Cell and Organ Radiosensitivity ……………….............. 52 Relative Biological Effectiveness………………............. 59 IAEA Table of Contents Topic Slide Biological Effects (High Doses)………………………. 63 Deterministic Effects…………………………………… 65 Acute Radiation Sickness……………………………... 69 Biological Effects (Low Doses)……………………….. 79 Stochastic Effects………………………………………. 80 Linear No Threshold Concept…………………………. 84 In Utero Radiation Effects……………………………… 86 Review Problems……………………………………….. 92 IAEA Living Organisms and Cellular Structure IAEA The Human Cell • The cell is the basic building block of life and the structural & functional unit of all living organisms. • Human beings originate from a single cell; the zygote. The zygote is formed by the union of a female egg and male sperm. • Rapid division and differentiation occur during prenatal development to form organs and tissues made up of many cells. • Humans are multicellular with trillions of cells. Cells can take in nutrients, produce energy, and perform specialized functions in the human body. IAEA Typical Cellular Structure • Organelles are subcomponents of cells with specific functions analogous to organs of the human body. • The main organelles are the mitochondria, nucleus, endoplasmic reticulum, golgi complex, lysosomes and ribosomes. • The cell membrane is a double layered membrane that surrounds the organelles and maintains the integrity of the cell. IAEA Cellular Components • Cytoplasm is the viscous gel-like substance that fills the cell and contains organelles. Most cellular activities occur in the cytoplasm. • Mitochondria are the sources of energy for cell functions through the metabolism of carbohydrates, fats, etc. • The endoplasmic reticulum processes molecules and transports them to specific destinations inside or outside of cells. IAEA Cellular Components • The golgi apparatus, or complex, processes and packages molecules for transport out of cells. • Lysosomes break down cellular waste materials to simpler compounds. • Ribosomes synthesize proteins, a macromolecule. IAEA Macromolecules • Cells contain macromolecules, organic molecules consisting of many smaller structural units linked together. • Four essential macromolecules found in the human body are: Proteins Lipids Nucleic Acids Carbohydrates IAEA Proteins • Proteins are amino acids linked together by peptide bonds. They are vital for metabolism and can function as enzymes to catalyze biochemical reactions. Proteins are important in cell signaling, immune response and cell structural and mechanical integrity. Protein Structure Amino Acid Polypeptide Intermediate Filament Protein IAEA Carbohydrates • • Carbohydrates are organic molecules composed of monosaccharides, simple sugars. They are a source of energy storage in living organisms. Monosaccharides can be linked together to form more complex carbohydrates which are classified as disaccharides, oligosaccharides, and polysaccharides. Deoxyribose and Ribose are monosaccharides. IAEA Nucleic Acids • Nucleic Acids are linked nucleotides consisting of a nitrogenous base, a five-carbon sugar and a phosphate group. Nucleotides joined together make up the structural units of DNA and RNA. Nucleotide IAEA DNA Lipids • Lipids are a fat-like substances that store needed energy for the human body. Lipids include fats, oils, steroids, phospholipids, fatty acids, etc. IAEA The Nucleus • The cell nucleus is the center of activities in a cell. • It is separated from cytoplasm by an inner and outer membrane • It houses chromosomes containing DNA. IAEA Chromosomes • Chromosomes are a condensed form of the nucleic acids and proteins in a cell. • Chromosomes are only visible during cell division. • Chromosomes have a constriction point called a centromere which divide them into a short arm (p) and a long arm (q). IAEA Deoxyribonucleic Acid (DNA) DNA is a nucleic acid found in the nucleus of most of the body's cells. It contains the genetic instructions required for cellular development and function. (Mature red bloods cells do not contain DNA since they do not have nuclei.) IAEA DNA Molecular Structure • DNA exists as two long, paired strands. The strands spiral around one another forming a double helix. • The strands are joined by chemical bases that can be arranged in countless ways. • The four nitrogenous bases found in DNA are adenine, thymine, guanine and cytosine. IAEA The order of the bases determines the messages to be conveyed, much as specific letters of the alphabet combine to form words and sentences. DNA Molecules • Nearly every cell in a person’s body has the same DNA.* • Each cell has 46 molecules of doublestranded DNA made up of 50 to 250 million bases. *DNA in cells can be altered due to mutations. IAEA Genes • A gene is a given segment along the DNA molecule. • Genes are found along chromosomes in linear order like beads on a string. • Each gene carries a particular set of instructions for the cell. • There are about 25,000 genes, and every gene is made up of thousands of chemical bases. IAEA Genes and Cellular Function • Cells use genes selectively. • Cells activate only the genes needed and suppress the rest. The unique selection of genes used by a cell gives that cell its character – making a brain cell different from a bone cell. • Genes also guide the cell life cycle including cell division. IAEA The Cell Cycle IAEA The Cell Cycle • Organisms must create new cells to continue life. • The series of events that take place in a cell leading to cell division and replication is referred to as the Cell Cycle. IAEA Stages of the Cell Cycle The three major phases of the cell cycle are interphase, mitosis, and cytokinesis. • Interphase is a preparation phase when the cell is taking in nutrients and growing to prepare for cell division. • Mitosis divides the chromosomes in a cell nucleus into two identical sets of nuclei. • Cytokinesis immediately follows mitosis producing two distinct daughter cells after the cytoplasm divides. IAEA Interphase Interphase occurs in the following three phases: • Gap 1 (G1) – The cell increases in size as it prepares for DNA synthesis. • Synthesis (S) – DNA replication occurs in this phase. • Gap 2 (G2) – The cell continues to grow in preparation for cell division. IAEA *G0, is a temporary or permanent resting phase when a cell is not dividing or preparing for division. For example, mature nerve cells (neurons) remain in G0. Mitosis and Cytokinesis Mitosis occurs in four major phases: • Prophase – chromosomes are visible and the nuclear membrane and nucleolus disappear. • Metaphase – chromosomes line up across center and spindle fibers attach. • Anaphase – chromosomes split and each half is pulled to opposite side of the cell. • Telophase - chromosomes cluster in the center of each cell and cell separation begins IAEA Nuclear membrane Nucleolus Chromosomes Cytokinesis completes the cell division process when the cytoplasm splits and two distinct daughter cells are formed. . Cell Cycle Checkpoints • Cell cycle checkpoints are found at various phases of the cell cycle to verify that the processes have been completed accurately before proceeding to the next phase. • Checkpoints assess DNA damage and can initiate a delay to allow for DNA repair or target a cell for destruction. IAEA Meiosis • Meiosis is a form of cell division that occurs with reproductive cells. • Two sequential cell divisions occur during meiosis resulting in four daughter cells. • The four daughter cells have half the number of chromosomes as the original cell and will develop into sperm and egg cells. IAEA Cellular Damage from Radiation IAEA Cellular Damage • Studies have shown that the cell nucleus is the most radiosensitive structure in the cell due to the damage that can occur to DNA. • Ionizing radiation can break bonds in DNA molecules resulting in mutations, cell death or carcinogenesis. • DNA is considered the critical biological target for ionizing radiation. IAEA Radiation Damage • Biological effects to the cell result from both direct and indirect action of radiation. • Direct effects are produced by the initial action of the radiation itself. • Indirect effects are caused by the later chemical action of free radicals and other radiation products. IAEA Direct Effect • • When radiation or secondary ions break the chemical bonds of critical biological molecules in human cells. This effect is more dominate for high linear energy transfer (LET) radiations such as alpha particles or neutrons. IAEA alpha ++ Indirect Effect • When radiation interacts with cellular water, it can break bonds that hold the water molecules together producing hydrogen (H) and hydroxyl (OH) free radicals. • Free radicals are highly reactive agents with unpaired electrons. • The free radicals can recombine or interact with other radicals and ions to form compounds that can damage the cell. IAEA Indirect Effect • One important free radical is the hydroxyl radical (OH•). • Two of these radicals can combine to form hydrogen peroxide (OH• + OH• H2O2); a powerful oxidizing agent that can attack and damage DNA by breaking chemical bonds. • Since cells are about 80% water, the indirect effect is believed to be more likely to occur than the direct effect. IAEA Radiation Damage to DNA The major types of DNA damage caused by bond breaks from ionizing radiation are • DNA base damage • Single - strand breaks • Double - strand breaks IAEA DNA Base Damage • DNA base damage is primarily caused by interactions of free radicals from the indirect effect with the nitrogenous bases. • DNA base damage can result in misrepairs which can cause mutations. IAEA Bonds are broken between the bases Single Strand Breaks • Radiation damage can cause a break in the bond in a single strand of DNA. • Single strand breaks are readily repaired using the opposite strand as template. • Incorrect repairs (misrepairs) can lead to mutations. Single strand breaks IAEA Single Strand Breaks Phosphate Single strand bond breaks can occur in the deoxyribose-base bond or the phosphatedeoxyribose bonds in DNA. Deoxyribose or sugar Phosphate – deoxyribose bond desoxyribose-base bond IAEA Double Strand Breaks • Breaks in both strands of DNA that are opposite, or separated by only a few base pairs are called Double Strand Breaks. • They can occur from the same particle, with enough energy to create two breaks or by two particles, one after the other, in a short enough time before repair of the first break. IAEA Double Strand Breaks • The phosphate-sugar bonds are broken on both strands of DNA double strand breaks. Phosphate –desoxyribose bond • High-LET radiations are responsible for most double strand breaks. • Double strand breaks are not easily repaired. IAEA Cellular Response to DNA Damage Cellular response following DNA damage will vary depending on the type of damage to the DNA. • Cells can repair DNA damage using repair mechanisms. Repairs are not always successful and misrepairs can occur. • Cellular death can occur resulting in the complete loss of cell function or a cell’s ability to proliferate. • Cells can enter a state of unregulated cell division. IAEA Cell Response to DNA Damage Cellular Metabolism Cell Cycle Arrest IAEA Viral Attacks Ionizing Radiation Transcriptional Program Activation Chemical Exposure DNA Repair (Different repair pathways can repair some DNA Damage. Misrepairs can occur leading to mutations) Replication Errors Apoptosis Cellular Death Cellular death can have different meanings depending on the type of cells affected by the radiation damage. • For differentiated cells like muscle & nerve cells, cellular death is defined as a loss of a specific function. • Proliferating cells can loose their ability to divide. The cell succeeds in dividing for several cycles, but ends up by decaying and dying. This is refereed to as delayed cell death or a loss of the cell’s reproductive integrity. • Necrosis can occurs when the cell cannot control subsequent decay. • Cells also can die via apoptosis; a programmed cell suicide process. IAEA Cell Necrosis IAEA Cell Response to DNA Damage Apoptosis, or programmed cell death can occur after radiation damage. Damaged cells are removed from the cellular population. IAEA Mutations and Aberrations • Although cells have the ability to repair DNA damage and do it continually, misrepair can result in mutations. • Not all DNA mutations are manifested as a disease or defect. • Damage to cellular DNA from radiation-induced breakage can lead to chromosome aberrations. IAEA Chromosome Aberrations • • Ionizing radiation can cause chromosomal and chromatid aberrations. Chromosome aberrations occur early in interphase before DNA duplication. Chromatid aberrations occur after DNA replication. Rings, dicentrics and fragments are the most common types of aberrations observed. IAEA fragment dicentric dicentric fragment ring Hereditary vs. Acquired Mutations Acquired mutations are caused by environmental factors such as diet, smoking, and radiation exposure. IAEA Radiation Induced Cancers • Cancer is uncontrolled cell growth. • All cancer is triggered by gene mutations. Genes that control the orderly replication of cells become damaged, allowing the cells to reproduce without restraint. • Cancer usually arises in a single cell. However, the cell's progression from normal to malignant appears to involve a series of mutations or changes. IAEA Stages of Cancer Development The three major stages of cancer development are : • Initiation – Initiators damage DNA which can lead to a cell mutation. • Promotion - Certain compounds can promote proliferation of a mutated cell which can give rise to a tumor. • Progression is the transformation of a tumor to a spreading malignancy. IAEA Mutations and Cancer Promotion Initiation Progression IAEA Radiosensitivity of Different Cells and Organ Systems IAEA Cell Radiosensitivity Generally, cells are more radiosensitive if they meet the following criteria: • Have high mitotic rate • Have a long mitotic future (i.e., undergo numerous divisions in the course of their lifetime) • Are of an unspecialized type (i.e., less differentiated) IAEA Cell Radiosensitivity Cells can be arranged in the following order of sensitivity: • • • • Blood forming stem cells Reproductive and GI stem cells Skin stem cells Mature nerve, muscle and brain cells IAEA more sensitive less sensitive Stem Cells • Stem cells are cells that retain the instructions to either continue developing undifferentiated or to form specific tissues • Their function is to provide specialized cells while ensuring a means of reproducing additional stem cells if needed. • For example, stem cells in the basal skin layer produce new skin cells. IAEA Blood Stem Cells IAEA Blood Forming Organs • Blood cells are produced by cells in the red bone marrow and include: • Red blood cells (carry oxygen to cells and carbon dioxide away) • White blood cells (fight infection) • Platelets (form clots) • Damage to stem cells in the red bone marrow inhibits the production of blood cells. IAEA Small Intestine • The small intestine contains stem cells that form epithelial lining. • These epithelial cells are constantly being replaced. • Damage to the stem cells prevents replacement of the epithelial lining and thus inhibits uptake of nutrients. IAEA Epithelial Lining Relative Biological Effectiveness (RBE) • Different types of radiation do not produce the same biological effects. • The ability of a given type of radiation to damage biological tissue is measured in terms of Relative Biological Effectiveness (RBE). • Radiation with a high linear energy transfer (LET) will produce a greater biological effect than lower LET radiations. • For example, a dose of 1 Gy from neutrons does not produce the same biological effect as a dose of 1 Gy from x-rays. IAEA Radiation Weighting Factors Radiation Weighting Factors are used in radiation protection to adjust for differing biological effects. Radiation Type and Energy Range wR Photons 1 Electrons and muons 1 Protons and charged pions 2 Alpha particles, fission fragments, heavy ions IAEA 20 Radiation Weighting Factors Radiation Type and Energy Range Neutrons IAEA wR A continuous function of neutron energy Equivalent Dose • Radiation weighting factors are used to calculate a biological meaningful quantity called Equivalent Dose. • The equivalent dose in a tissue T is calculated using the following: HT = 𝑹 wR DT,R where DT,R is the absorbed dose averaged over the tissue or organ T, due to radiation R. • Absorbed dose is a measure of energy deposited by radiation in a given mass of any material expressed in the SI unit of Gray (Gy). Absorbed dose applies to all ionizing radiations at all energies in all media, including human tissue. IAEA Biological Effects from High Doses of Radiation IAEA Biological Effects Overview Radiation damage to DNA begins at the cellular level but can eventually cause harmful tissue reactions which can effect organs and the whole body. Atom Molecule Radiation ionizes atoms (knocks out electrons) IAEA Deterministic Effects • Harmful tissue reactions that occur at relatively high doses are called deterministic effects. • Deterministic effects have a dose threshold and will not occur at doses below the threshold. The severity of the effect increases with dose. • Radiation damage (serious malfunction or cell death) to collective populations of cells in given tissue must occur before the effects appear. • Deterministic effects can appear early (days to weeks) or later (months to years) after exposure. • These effects can be prevented altogether if dose is kept below the threshold. IAEA Deterministic Effects • Doses below 100 mGy delivered over a short period of time do not result in measurable changes to biological tissues. • Examples of deterministic effects are: • • • • • Blood count changes Sterility (temporary or permanent) Skin Burns Cataracts Acute Radiation Sickness IAEA Severity Deterministic Dose Response Relationship The severity of the effect increases as the dose increases. For each deterministic effect there is a threshold dose below which the effect may not occur. Dose Threshold IAEA Typical Deterministic Dose Response Curve The dose threshold will vary according to the health, age and physical characteristics of the exposed individuals. However, there is a threshold where 100% of the exposed population experiences the effect. Dose (Gy) Note: Since the threshold values vary, ranges are often reported. Some ICRP publications publish the threshold doses for deterministic effects at a 1% incidence rate. IAEA Acute Radiation Sickness • Acute Radiation Sickness (ARS) results from a large dose of radiation delivered to the whole body over a very short time period • Signs and symptoms of ARS will vary based on the amount, duration and type of exposure. • ARS can be divided into three syndromes: • Hematopoietic or Blood Syndrome • Gastrointestinal (GI) Syndrome • Central Nervous System (CNS) Syndrome IAEA Hematopoietic (Blood Syndrome) • Hematopoietic syndrome develops at doses greater 1 – 2 Gy. • Radiation damage halts the ability of blood stem cells to reproduce. This diminishes the subsequent supply of red blood cells, white blood cells and platelets. • Signs and symptoms include nausea, vomiting, malaise and fatigue. Loss of hair (epilation) occurs during the 2nd or 3rd week after exposure. Death is likely to occur within 1 – 2 months after exposure for doses greater than 2 Gy. IAEA Blood Syndrome Lymphocytes (Percent of Normal) A decrease in blood lymphocytes is the first sign of hematopoietic syndrome. The decrease appears within a few hours or days after irradiation. 50-75% of the lymphocytes are destroyed at doses above 2-3 Gy. Lymphocyte Changes in Humans from Accidental Radiation Exposure as a Function of Dose Time after Exposure (Days) IAEA GI Syndrome • GI syndrome occurs at does above 7 - 10 Gy. • The tissue at risk is epithelial lining of small intestine. • Effects include nausea, vomiting, and diarrhea. • Death is almost certain within 3-14 days at doses over 10 Gy. • Causes of death include infection, bleeding, dehydration, electrolyte imbalance, and circulatory collapse. IAEA CNS Syndrome • CNS Syndrome occurs at doses about 15 Gy. • The organ at risk is the brain. • Effects include lethargy, convulsions, tremors, loss of muscle control, and coma (in addition to effects from other syndromes). • Death will occur within hours to a few days for doses greater than 50 Gy. • The causes of death include respiratory and circulatory collapse. IAEA Lethal Dose (LD) 50/60 • The LD 50/60 is defined as the acute dose at which 50% of the exposed population will die within 60 days without medical treatment. • The LD 50/60 for human beings is about 3-5 Gy for a whole body dose. • Acute doses above about 10 Gy are usually fatal, even with medical treatment. IAEA LD 50/60 IAEA Range of Deterministic Effects Dose (gray) Effect 0.25 - 0.50 Detectable changes in blood chemistry but no physical symptoms. 1- 3 Some physical symptoms - skin reddening and loss of hair. at the high end of the range, vomiting is caused shortly after exposure. 3 - 4.5 Vomiting is first symptom. Major loss in ability to produce blood. 4-5 (LD50/60) Death to 50% of the population within 60 days if no medical treatment. 4.5 - 10 At upper end, bone marrow transplants needed. Fatal within one month without medical care. 10 - 50 Vomiting, loss of blood production, failure of GI system. Fatal within several days. > 50 Central nervous system failure. Death within hours or days. IAEA Deterministic Thresholds for Specific Organs & Tissue After Whole Body Gamma Exposure Organ or tissue Absorbed Dose (Gy) Deterministic effects Type of effect Time of occurrence Skin 3-6 Main Phase of skin reddening 1 – 4 weeks Skin 4 Temporary Hair Loss 2 – 3 weeks Eyes 1.5 Cataracts (Visual several years Impairment) Ovaries 3 Permanent Sterility < 1 week Testes 6 Permanent sterility 3 weeks IAEA Deterministic Effects for Partial Body Irradiation • When only a small portion of the body receives high doses, local effects will be observed, but Acute Radiation Sickness will not occur. • Critical tissues are the skin, thyroid, lung, lenses of the eye and gonads, etc. IAEA Biological Effects from Low Doses of Radiation IAEA Stochastic Effects • The principal effects of doses < 100 mSv are nonlethal cell mutations. • If the cell is not killed but the DNA is changed, it may give rise to a mutated cell. • If any cell, capable of dividing, is damaged by radiation, a cancer may eventually develop. IAEA Stochastic Effects • Stochastic effects generally occur without a dose threshold and the probability of occurrence of the effect is a function of dose. The severity of stochastic effects is independent of the dose received. • Stochastic effects include: • Radiation Induced Cancers • Hereditary genetic effects (not proven in humans) IAEA Stochastic Cancer Effects • Radiation induced cancers have been well documented from studies of Atomic Bomb survivors, uranium miners and early users of radiation in the medical field. • Radiation can produce cancers in blood forming tissues, skin, bone, lung, thyroid and connective tissues. • The majority or radiation induced cancers have a latency period of at least 10 years. Leukemia, cancer of the blood, has a shorter latency period of ~2 - 4 years after exposure. IAEA Stochastic Hereditary Effects • If the damage caused by radiation occurs in the reproductive cells, it may be transmitted and become manifested as hereditary disorders in the descendents of the exposed individual. • These effects have not been proven in humans, but experimental studies on plants and animals suggest that effects can occur. Health effects may range from undetectable to gross malformation, or loss of function to premature death. IAEA Linear Non-Threshold Model • The Linear Non-Threshold (LNT) Model is a dose response model, based on the assumption that in the low dose ranges, the risk or probability of developing stochastic effects increases with dose. IAEA Dose-Response Relationship for Stochastic Effects The Linear Non- Threshold (LNT) Model : • Every increment of radiation, no matter how small increases the probability or risk of developing a stochastic effect. • The dose response is linear. IAEA In Utero Radiation Effects IAEA In Utero Radiation Effects • The human embryo and fetus are highly sensitive to the effects of radiation. • Radiation sensitivity varies according to the stage of pre-natal development. The embryo/fetus is more sensitive during the period of organogenesis. • In Utero effects are different from hereditary effects because the embryo/fetus is being irradiated. IAEA In Utero Radiation Effects The principal effects of in utero exposure are: • Growth retardation • Mental retardation • Childhood cancer • Developmental abnormalities IAEA Growth Retardations • With children, growth retardations of the brain and skull have been found very pronounced after prenatal radiation doses in the order of 0.5 Gy. • The high radiosensitivity of the central nervous system can be explained by the fact that the development of the brain takes the longest time and is most complex. • For atomic bomb survivors a reduced circumference of the head has been observed. IAEA Mental Retardation • Severe mental retardation can occur when the brain is forming during the early stage of pre-natal development. • A study of about 1600 children exposed in-utero at Hiroshima and Nagasaki to various radiation doses and at various developmental stages identified clinically severe mental retardation in some dose groups. IAEA Cancer Development from In Utero Radiation Exposure • Studies have shown that there is an increased risk of developing childhood cancers of all types following inutero irradiation. • The lifetime cancer risk following in-utero exposure is similar to the risk following irradiation in early childhood, i.e. about three times that of the population as a whole. IAEA REVIEW PROBLEMS IAEA Problem 1 What is the critical biological target for ionizing radiation? IAEA Problem 2 The radiation __________ effect occurs when DNA is damaged by free radicals or other reactants created by radiation interaction with cellular water. a) Direct b) Indirect c) Stochastic IAEA Problem 3 Cells can repair a portion of radiation damage. a) True b) False IAEA Problem 4 When DNA is damaged by radiation, it is always manifested as a disease or defect. a) True b) False IAEA Problem 5 Most cancers originate from how many cells? a) One b) Two c) Five IAEA Problem 6 ______ is a free radical produced from the indirect effect of radiation interacting with cellular water. a) H2O2 b) OH c) H2O IAEA Problem 7 ______ is an oxidizing agent that is produced from the chemical actions associated with the indirect effect of radiation. a) H2O2 b) OH c) H2O IAEA Problem 8 Cells are more radiosensitive if they have a ______ division rate. a) low b) moderate c) high IAEA Problem 9 Cells are more radiosensitive if they are a) unspecialized b) more differentiated c) specialized IAEA Problem 10 _____ and ____ are examples of stochastic effects of radiation exposure. a) Cancer and hereditary genetic effects b) ARS and cancer c) Erythema and hereditary genetic effects IAEA Problem 11 The linear non-threshold concept means the probability of ___________ effects occurring increase with dose. a) Deterministic b) Indirect c) Stochastic IAEA Problem 12 Hematopoietic, GI and _________ syndromes are all part of acute radiation sickness. a) Central Nervous System b) Erythema c) Cancer IAEA Problem 13 What is the approximate value of LD 50/60? a) b) c) d) IAEA 1 - 2 gray 2 - 3 gray 3 - 5 gray 9 - 10 gray Problem 14 Hereditary genetic effects are _________ effects of ionizing radiation exposure. a) threshold b) deterministic c) stochastic IAEA Review Problem Solutions 1. 2. 3. 4. 5. 6. 7. DNA b) Indirect True False a) one b) OH b) H2O2 IAEA 8. 9. 10. 11. 12. 13. 14. c) high a) unspecialized a) cancer and hereditary genetic effects c) stochastic a) Central Nervous System C) 3 - 5 gray C) stochastic END OF BIOLOGY AND RADIATION EFFECTS IAEA