CHAPTER 5 BIOLOGICAL EFFECTS OF IONIZING RADIATION PAGE

CHAPTER 5BIOLOGICAL EFFECTS OF IONIZING RADIATIONPAGEI.Introduction . 5-3II.Mechanisms of Radiation Damage . 5-3A.Direct Action . 5-3B.Indirect Action . 5-3III.Determinants of Biological Effects . 5-4A.Rate of Absorption . 5-5B.Area Exposed . 5-5C.Variation in Species and Individual Sensitivity . 5-5D.Variation in Cell Sensitivity. 5-5IV.The Dose-Response Curve . 5-6V.Pattern of Biological Effects . 5-7A.Prodromal Stage . 5-7B.Latent Period . 5-7C.Period of Demonstrable Effects . 5-7D.Recovery Period . 5-7VI.Short Term Effects . 5-8A.Acute Radiation Syndrome . 5-81. Prodrome . 5-82. Latent Stage. 5-83. Manifest Illness Stage . 5-84. Recovery or Death. 5-8B.Localized Exposure . 5-10VII.Long Term Effects . 5-10A.Introduction . 5-10B.Carcinogenic Effects . 5-111. Possible Carcinogenic Effects . 5-112. Human Evidence for Radiation Carcinogenesis . 5-133. Significance of Human Studies on Radiation Carcinogenesis . 5-16C.Cataractogenic Effects . 5-17D.Lifespan Shortening . 5-171.Mechanisms . 5-172.Human Evidence . 5-18E.Genetic Effects . 5-181.Background . 5-182.Observing Mutations . 5-19RSSC BIOLOGICAL EFFECTS OF IONIZING RADIATION 08/115-1

3.4.5.Animal Evidence of Genetic Effects . 5-21Human Evidence of Genetic Effects . 5-21Health Significance of Genetic Mutations . 5-22VIII.Embryological Effects . 5-23A.Embryological Effect vs. Stage of Pregnancy . 5-23B.Human Evidence for Embryological Effects . 5-24C.The Problem of Unsuspected Pregnancy . 5-24IX.Instruction Concerning Prenatal Radiation Exposure . 5-25A.Introduction . 5-25B.Discussion . 5-25C.Regulatory Position . 5-25D.Effect on the Embryo/Fetus of Exposureto Radiation and other Environmental Hazards . 5-261.Radiation Risks . 5-262.Nonradiation Risks. 5-27E.Advice for the Employee & Employer . 5-29F.Internal Hazards Pertaining to Prenatal Exposure . 5-311.Tritium . 5-312.Organically Bound Tritium and Carbon . 5-323.Iodine . 5-33X.Background Radiation. 5-33XI.References . 5-365-2RSSC BIOLOGICAL EFFECTS OF IONIZING RADIATION 08/11

BIOLOGICAL EFFECTS OF IONIZING RADIATIONI.INTRODUCTIONThe fact that ionizing radiation produces biological damage has been known for many years.The first case of human injury was reported in the literature just a few months followingRoentgen's original paper in 1895 announcing the discovery of x-rays. As early as 1902, thefirst case of x-ray induced cancer was reported in the literature.Early human evidence of harmful effects as a result of exposure to radiation in large amountsexisted in the 1920's and 30's, based upon the experience of early radiologists, minersexposed to airborne radioactivity underground, persons working in the radium industry, andother special occupational groups. The long-term biological significance of smaller, repeateddoses of radiation, however, was not widely appreciated until relatively recently, and most ofour knowledge of the biological effects of radiation has been accumulated since World WarII.II.MECHANISMS OF RADIATION DAMAGERadiation damage starts at the cellular level. Radiation which is absorbed in a cell has thepotential to impact a variety of critical targets in the cell, the most important of which is theDNA. Evidence indicates that damage to the DNA is what causes cell death, mutation, andcarcinogenesis. The mechanism by which the damage occurs can happen via one of twoscenarios.A.Direct ActionIn the first scenario, radiation may impact the DNA directly, causing ionization of theatoms in the DNA molecule. This can be visualized as a “direct hit” by the radiationon the DNA, and thus is a fairly uncommon occurrence due to the small size of thetarget; the diameter of the DNA helix is only about 2 nm. It is estimated that theradiation must produce ionization within a few nanometers of the DNA molecule inorder for this action to occur.B.Indirect ActionIn the second scenario, the radiation interacts with non-critical target atoms ormolecules, usually water. This results in the production of free radicals, which areatoms or molecules that have an unpaired electron and thus are highly reactive. Thesefree radicals can then attack critical targets such as the DNA (Figure 1). Because theyare able to diffuse some distance in the cell, the initial ionization event does not haveto occur so close to the DNA in order to cause damage. Thus, damage from indirectaction is much more common than damage from direct action, especially for radiationthat has a low specific ionization.RSSC BIOLOGICAL EFFECTS OF IONIZING RADIATION 08/115-3

Figure 1: Mechanisms of Radiation DamageWhen the DNA is attacked, either via direct or indirect action, damage is caused to thestrands of molecules that make up the double-helix structure. Most of this damage consists ofbreaks in only one of the two strands and is easily repaired by the cell, using the opposingstrand as a template. If, however, a double-strand break occurs, the cell has much moredifficulty repairing the damage and may make mistakes. This can result in mutations, orchanges to the DNA code, which can result in consequences such as cancer or cell death.Double-strand breaks occur at a rate of about one double-stand break to 25 single-strandbreaks. Thus, most radiation damage to DNA is reparable.III.DETERMINANTS OF BIOLOGICAL EFFECTSA.Rate of AbsorptionThe rate at which the radiation is administered or absorbed is most important in thedetermination of what effects will occur. Since a considerable degree of recoveryoccurs from the radiation damage, a given dose will produce less effect if divided(thus allowing time for recovery between dose increments) than if it were given in asingle exposure.5-4RSSC BIOLOGICAL EFFECTS OF IONIZING RADIATION 08/11

B.Area ExposedThe portion of the body irradiated is an important exposure parameter because thelarger the area exposed, other factors being equal, the greater the overall damage tothe organism. This is because more cells have been impacted and there is a greaterprobability of affecting large portions of tissues or organs. Even partial shielding ofthe highly radiosensitive blood-forming organs such as the spleen and bone marrowcan mitigate the total effect considerably. An example of this phenomenon is inradiation therapy, in which doses which would be lethal if delivered to the wholebody are commonly delivered to very limited areas, e.g., to tumor sites.Generally when expressing external radiation exposure without qualifying the area ofthe body involved, whole-body irradiation is assumed.C.Variation in Species and Individual SensitivityThere is a wide variation in the radiosensitivity of various species. Lethal doses forplants and microorganisms, for example, are usually hundreds of times larger thanthose for mammals. Even among different species of rodents, it is not unusual for oneto demonstrate three or four times the sensitivity of another.Within the same species, individuals vary in sensitivity. For this reason the lethaldose for each species is expressed in statistical terms, usually for animals as theLD50/30 for that species, or the dose required to kill 50 percent of the individuals in alarge population in a thirty day period. For humans, the LD50/60 (the dose required tokill 50 percent of the population in 60 days) is used because of the longer latentperiod in humans (see section V). The LD50/60 for humans is estimated to beapproximately 300-400 rad for whole body irradiation, assuming no treatment isgiven. It can be as high as 800 rad with adequate medical care. It is interesting to notethat the guinea pig has a LD50 similar to humans.D.Variation in Cell SensitivityWithin the same individual, a wide variation in susceptibility to radiation damageexists among different types of cells and tissues. In general, those cells which arerapidly dividing or have a potential for rapid division are more sensitive than thosewhich do not divide. Further, cells which are non-differentiated (i.e., primitive, ornon-specialized) are more sensitive than those which are highly specialized. Withinthe same cell families, then, the immature forms, which are generally primitive andrapidly dividing, are more radiosensitive than the older, mature cells which havespecialized in function and have ceased to divide. This radiosensitivity is defined asthe "Law of Bergoniè and Tribondeau". One exception to this law is maturelymphocytes, which are highly radiosensitive.Based upon these factors, it is possible to rank various kinds of cells in descendingorder of radiosensitivity. Most sensitive are the white blood cells called lymphocytes,followed by immature red blood cells. Epithelial cells, which line and cover bodyRSSC BIOLOGICAL EFFECTS OF IONIZING RADIATION 08/115-5

organs, are of moderately high sensitivity; in terms of injury from large doses ofwhole-body external radiation, the epithelial cells which line the gastrointestinal tractare often of particular importance. Cells of low sensitivity include muscle and nerve,which are highly differentiated and do not divide.IV.THE DOSE-RESPONSE CURVEFor any biologically harmful agent, it is useful to correlate the dosage administeredwith the response or damage produced, in order to establish acceptable levels ofexposure. "Amount of damage" in the case of radiation might be the frequency of agiven abnormality in the cells of an irradiated animal, or the incidence of somechronic disease in an irradiated human population. In plotting these two variables, adose-response curve is produced. With radiation, an important question has been thenature and shape of this curve. Two possibilities are illustrated in Figures 2a and 2b.Figure 2a represents a typical "threshold" curve. The point at which the curveintersects the abscissa is the threshold dose, i.e., the dose below which there is noresponse. If an easily observable radiation effect, such as reddening of the skin, istaken as a "response," then this type of curve is applicable. The first evidence of theeffect does not occur until a certain minimum dose is reached, although unobservedeffects may exist.Figure 2b represents a linear, non-threshold relationship, in which the curve intersectsthe abscissa at the origin. Here it is assumed that any dose, no matter how small,involves some degree of response. There is some evidence that the carcinogeniceffects of radiation constitute a non-threshold phenomenon, so one of the underlying(and prudent) assumptions in the establishment of radiation protection guidelines hasbeen the existence of a non-threshold effect. Thus, some degree of risk is assumedwhen large populations of people are exposed to even very small amounts ofradiation. This assumption often makes the establishment of guidelines for acceptableradiation exposure a complex task, since the concept of "acceptable risk" comes intoplay, in which the benefit to be accrued from a given radiation exposure must beweighed against its hazard.Figure 2(a)5-6Figure 2(b)RSSC BIOLOGICAL EFFECTS OF IONIZING RADIATION 08/11