59 CHAPTER 3. BIOLOGICAL EFFECTS AND HAZARDS OF RADIATION EXPOSURE J. F. Boas and S. B. Solomon Australian Radiation Laboratory ABSTRACT Radiation induced carcinogenesis and mutagensis form the main risk to health from exposure to low levels of radiation. This risk effects can be at least qualitatively understood by considering the effects of radiation on cell DNA. Whilst exposure to high levels of radiation results in a number of identifiable effects, exposure to low levels of radiation may result in effects which only manifest themselves after many years. Risk estimates for low levels of radiation have been derived on the basis of a number of assumptions. In the case of uranium mine workers a major hazard arises from the inhalation of radon daughters. Whilst the correlation between radon daughter exposure and lung cancer incidence is well established, the numerical value of the risk factor is the subject of controversy. ICRP 50 gives a value of 10 cases per 10 person-years at risk per WLM (range 5-15 x 10 PYR WLM ). The effect of smoking on lung cancer incidence rates amongst miners is also controversial. Nevertheless, smoking by miners should be discouraged. INTROOUCUON The biological effects of ionizing radiation arise from the changes induced by radiation in the cells of the body. These changes result 1n either cell death, which occurs when the cell is unable to produce viable daughters on cell division, or in cell damage. In the case of cell damage, the cell can survive and divide, but may transmit an induced abnormality to future generations. On a molecular level, the energy lost by radiation in passing through a cell causes ionization of water molecules along the track of the particle or photon. These ions are then able to interact with the DNA molecules of the nuclear chromosomes of the cell, and cause breaks in the strands of the DNA double helix, which carries the genetic code. If only one 60 strand is broken, the cell is able to repair the break correctly within a few minutes, using the unbroken strand as a template. If both strands are broken in approximately the same position and at the same time (i.e. before repair of one can take place), there is no template and the strands may either not rejoin or may be rejoined with an incorrect sequence of base pairs. This incorrect sequencing will affect the structure (and hence the function) of the proteins of the cell, which are formed using the information carried by the DNA molecule. The molecular model of the effects of radiation allows us to explain a number of important biological observations, at least on a qualitative basis. These include (a) The acute effects of high doses of radiation, which result from substantial numbers of cell deaths, probably due to double strand breaks which are not repaired prior to cell division. (b) Cancer induction, which probably results from incorrect repair of the DNA molecule and the subsequent breakdown of the enzyme mechanisms controlling cell function and division. (c) Genetic effects, which result from the transmission of incorrectly repaired DNA molecules to future generations. (d) The differences between the dose-response relationships postulated for high LET radiation (a-particles, protons and neutrons) and low LET radiation (photons and electrons) and the greater effectiveness of high LET radiation 1n Inducing radiation effects. (e) The variation in the radlosensitivity of different organs or tissues 1s related to the rate at which the cells divide and the rate at which DNA repair can take place within a cell. Some of these observations will be discussed in more detail 1n subsequent sections. However, 1t should be noted at this point that few areas of biology generate more controversy than those associated with the questions of dose-response curves and thresholds at low doses. Since even persons who are exposed as a result of their occupation are unlikely to receive lifetime occupational dose equivalents 1n excess of around 100 mSv (Thorne 1987), most radiation exposures, to both radiation workers and to members of the public are in the low dose category. •TlT 'Z-li 61 J CLASSIFICATION AND NATURE OF RADIATION EFFECTS The effects of radiation are classified as somatic or genetic and '*> stochastic or non-stochastic. Somatic effects are those which appear in the exposed person. They include acute short-term effects, which appear as a result of a single large exposure (e.g. nausea, infection) or late effects (e.g. i cancer, cataract formation). Genetic effects are those which appear in future generations. They may be inconsequential to the individual of a later generation or may result in a serious handicap. Stochastic effects are those which occur in a statistical manner, i.e. the probability of the effect occurring is a function of dose and has no threshold (i.e. there is no dose below which the effect does not occur). Cancer induction and the induction of genetic defects are normally considered to be stochastic effects. Given a population exposed to a known amount of ionizing radiation, it is possible to estimate how many cancers will be induced but not to identify which particular individuals will contract cancer as a result of that exposure. The severity of a stochastic effect is k* independent of the dose received. Non-stochastic effects are those where the severity is a function of dose and where there is a clear causal relationship between the exposure and the effect in a particular individual. There is usually 4 a threshold below which no effect is observed. An example of a non-stochastic effect 1s skin reddening e.g. as in a sunburn. Effects of High Radiation Doses - The Acute Radiation Syndrome i The acute effects of radiation exposure have been documented and are i summarized in Table 1 for the case of a single, large, short-term, whole-body dose of gamma radiation (see e.g. Turner 1986). % * - -L I**"**- 62 Table 1 Acute Radiation Syndrome for Gamma Radiation Dose Symptoms Remarks (Sievert) 0 - 0.2b None No detectable effects. 0.2b - 1 Mostly none. A few persons may Bone marrow damaged; decrease in exhibit mild prodromal symptoms, red and white blood-cell counts such as nausea and anorexia and platelet count. Lymph nodes and spleen injured; lymphocyte count decreases. I - 3 Mild to severe nausea, malaise, Haematologic damage more severe. anorexia, infection. Recovery probable, though not assured. 3-6 Severe effects as above, plus Fatalities will occur - about haemorrhaging, infection, 50°/o in the range 4.5-5 Sv. diarrhea, epilation, temporary sterility. More than 6 Above symptoms plus impairment Death expected. of central nervous system; incapacitation at doses above 10 Sv. Ihe acute radiation syndrome exhibits four sequential stages, where the individual exhibits symptoms which depend on the magnitude of the dose. up to 48 hours after exposure (the prodromal period), tiredness, nausea, sweating, anorexia. 48 hours to 2 or 3 weeks after exposure (latent period), general wel1-being. 2 or 3 weeks 1o 6 to 8 weeks after exposure (manifest Illness stage), damage to the haematological system as shown by haemorrhaging and infection, fever, loss of hair (epilation), lethargy, perception disturbances, diarrhoea. Death may also occur during this period. several weeks or months later, a recovery stage occurs. 63 An acute, whole body gamma ray dose of around 5 Sv is regarded as being fatal to 50Vo of the population within 30 days. This is designated as the LD50/30 dose. Delayed Somatic Effects These are effects which are only manifested many years after exposure of the individual concerned. The most important of these is the production of cancer. However, there a number of other effects which may occur, including degenerative changes of specific organs and organ systems, cataracts, impairment of fertility and growth and developmental defects in fetuses and young children. The ICRP has set special limits on exposures to the lens of the eye and on the exposures to women during the gestation period (see below). Genetic Effects Studies on various species (e.g. the mouse or the or the fruit-fly Drosophiia) have given evidence for the dose dependence of the induction of genetic abnormalities. However, there appears to be no reliable data for similar occurrences in man. Part of the difficulty in arriving at reliable estimates of the genetic risk arises because the normal incidence of genetic abnormalities is approximately 10°/,, of all live births. (Not all of the defects are necessarily harmful or fatal). In the case of the A-bomb survivors, extensive studies have failed to provide clear evidence of inherited abnormalities in children born since 1945. Even though there does appear to be evidence of a slight increase in the incidence of several types of genetic defect, the overall statistical evidence is assessed as being not reliable enough (Mettler and Moseley 1985, p60). However, there is evidence for an increased frequency of mental retardation in children exposed in utero to the atomic bomb radiation at Hiroshima and Nagasaki (Otake and Schull, 1984). Both UNSCEAR (1982) and BEIR (1980) have compiled extensive reports on the genetic effects of ionizing radiation. These reports are broadly consistent -3 with the estimates of risk given by ICRP (1977) of 4 x 10 serious hereditary effects in the first two generations per parental Sv. The risks to future generations are regarded as being twice this figure. The figure given above, which corresponds to 20 cases per generation per million persons exposed to 10 mSv (1 rem), may be compared with the incidence of serious genetic defects not attributable to radiation of ca. 10,000 per million live births and of another 90,000 per million live births of Irregularly inherited genetic disorders (Mettler and Moseley 1985 p56, BEIR 1980 p85).