Current problems of estimation of genetic risk of human exposure to radiation

The methodology of assessing the genetic risk of radiation exposure is based on the concept of "hitting the target" in development of which N.V. Timofeeff-Ressovsky has played and important role. To predict genetic risk posed by irradiation, the UN Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) has worked out direct and indirect methods of assessment, extrapolational, integral and populational criteria of risk analysis that together permit calculating the risk from human exposure on the basis of data obtained for mice. Laboratory mice are the main objects in studying radiation mutagenesis due to the fact that the data on the frequency of radiation-induced human mutations are rather scarce. The method of doubling dose based on the determination of a dose doubling the level of natural mutational process in humans is the main one used to predict the genetic risk. The evolution of views about the genetics risk of human exposure to radiation for last 40 years is considered. Till 1972 the main model for assessing the genetic risk was the "human/mouse" model (the use of data on the spontaneous human variability and data on the frequency of induced mutations in mice). In the period form 1972 till 1994 the "mouse/mouse" model was intensively elaborated in many laboratories. This model was also used in this period by UNSCEAR experts to analyze the genetic risk from human irradiation. Recent achievements associated with the study of the molecular nature of many hereditary human diseases as well as the criticism of number fundamental principles of the "mouse/mouse" model for estimating the genetic risk on a new basis. The estimates of risk for the different classes of genetic diseases have been obtained using the doubling-dose method. The estimate of doubling dose used in the calculations is 1 Gy for low dose/chronic low-LET radiation conditions.     

Issues and epidemiological evidence regarding radiation-induced thyroid cancer.

The available information on the induction of thyroid cancer in humans by ionizing radiation is summarized and weaknesses or gaps in assessing risk are identified. Issues to be addressed include: average estimates of thyroid cancer risk from external irradiation, the effects of age on thyroid cancer induction, shape of the dose-response curve for acute irradiation, magnitude of risk at low doses, effects of dose fractionation or dose protraction, the relative effectiveness of iodine-131 (131I) in inducing thyroid cancer compared to external radiation, the temporal course of radiogenic thyroid cancer risk, mortality caused by thyroid cancer, host-susceptibility factors for radiogenic thyroid cancer, and biological factors in risk. It is concluded that the most important needs are to obtain more information on thyroid cancer risks following low-level or highly fractionated radiation exposures and following 131I exposure in children.     

Out-of-field organ doses and associated risk of cancer development following radiation therapy with photons

Innovations in cancer treatment have contributed to the improved survival rate of these patients. Radiotherapy is one of the main options for cancer management nowadays. High doses of ionizing radiation are usually delivered to the tumor site with high energy photon beams. However, the therapeutic radiation exposure may lead to second cancer induction. Moreover, the introduction of intensity-modulated radiation therapy over the last decades has increased the radiation dose to out-of-field organs compared to that from conventional irradiation. The increased organ doses might result in elevated probabilities for developing secondary malignancies to critical organs outside the treatment volume. The organ-specific dosimetry is considered necessary for the theoretical second cancer risk assessment and the proper analysis of data derived from epidemiological reports. This study reviews the methods employed for the measurement and calculation of out-of-field organ doses from exposure to photons and/or neutrons. The strengths and weaknesses of these dosimetric approaches are described in detail. This is followed by a review of the epidemiological data associated with out-of-field cancer risks. Previously published theoretical cancer risk estimates for adult and pediatric patients undergoing radiotherapy with conventional and advanced techniques are presented. The methodology for the theoretical prediction of the probability of carcinogenesis to out-of-field sites and the limitations of this approach are discussed. The article also focuses on the factors affecting the magnitude of the probability for developing radiotherapy-induced malignancies. The restriction of out-of-field doses and risks through the use of different types of shielding equipment is presented.     

Evaluation of genetic radiation hazards in man: History,present status and perspectives

The evaluation of genetic radiation hazards in man is an ongoing scientific enterprise from about the mid-1950s. Since estimates of genetic risks are essential for providing a basis for protecting our genetical endowment and since strictly relevant human data are limited, there is no alternative at present but to use the data from mouse and certain non-human primates. This paper reviews the general principles and methods that have thus far been used, appraises the evolution of the conceptual framework, the data base and the assumptions involved, presents current estimates of genetic risks and provides some perspective of the advances that are likely to be made in the near future. Currently, risk estimates are made using the so-called “direct method” and the “doubling dose method”. Both these methods involve a number of assumptions and consequent uncertainties. With the direct method, it is now estimated that following low LET, low dose-rate or low-dose irradiation of males, there will be (i) about 10–20 cases of affected children per million births per rad of exposure, who will suffer from the effects of induced mutations having dominant effects and (ii) about 1 to 10 cases of congenitally malformed children (again per million births per rad), a consequence of the induction of reciprocal translocations. For irradiation of females under similar conditions, the estimated risks are 0–9 and 0–3 affected children per million births per rad, these being the consequence of induction of dominant mutations and of reciprocal translocations, respectively. The doubling dose method is used to estimate risks to a population under continuous irradiation. If the population is exposed to low LET irradiation at a rate of 1 rad/generation (1 generation = 30 years), the expected total increments in the frequencies of genetic diseases are about 20 cases per million births in the first generation and about 150 cases per million births at equilibrium. These expected increments are very small fractions of the spontaneous prevalence of genetic and partially genetic disorders, currently estimated to be about 10.6 %.     

Effects and consequences of prenatal irradiation

After a brief introduction about the historic development of risk estimates and maximum permissible doses of ionizing radiation, the risks of prenatal irradiation are discussed. Experimental data mainly obtained with mice indicate that the most important risk exists during the period of organogenesis and concerns the induction of malformations. Although in man this period lies between about 10 and 80 days after fertilization for most organs, the main development of the brain occurs later, namely between the 8th and 15th week after conception. Data from Japanese victims of the atomic bomb explosions above Hiroshima and Nagasaki indicate that during development the brain is the most sensitive organ to irradiation and maximal sensitivity is found between the 8th and 15th week after fertilization. A dose of one Gray received during this period induces a severe mental retardation in about 45% of the newborns. The dose response relationship is not significantly different from a linear one without a threshold dose. Studies of intelligence and school performance have shown that 1 Gray received during the 8th-15th week causes a shift of the average intelligence of about 30 points. Irradiation before the 8th week and after the 25th week had no effect on intelligence or mental retardation. During the 16th and 25th week sensitivity was about one fourth of that during the 8th-15th week. Although the irradiation of the embryo and fetus should be avoided as much as possible, the new data have led to an abandonment of the so-called 10-day rule. Generally an accidental irradiation of the embryo or fetus of less than 5 cGy is not considered as a medical indication for abortion. Retrospective studies showed that mothers from children who died from leukemia or other childhood tumors, had been subjected to a diagnostic irradiation of the pelvis or lower abdomen more frequently than mothers from children that did not develop a tumor. It has been estimated that prenatal sensitivity for induction of leukemia and tumors is higher than sensitivity after birth. However, it is still in discussion, whether the relationship between prenatal irradiation and a higher incidence of tumors is of a causal nature.     

The effect of dose rate on radiation-induced neoplastic transformation in vitro by low doses of low-LET radiation

The dependence of the incidence of radiation-induced cancer on the dose rate of the radiation exposure is a question of considerable importance to the estimation of risk of cancer induction by low-dose-rate radiation. Currently a dose and dose-rate effectiveness factor (DDREF) is used to convert high-dose-rate risk estimates to low dose rates. In this study, the end point of neoplastic transformation in vitro has been used to explore this question. It has been shown previously that for low doses of low-LET radiation delivered at high dose rates, there is a suppression of neoplastic transformation frequency at doses less than around 100 mGy. In the present study, dose-response curves up to a total dose of 1000 mGy have been generated for photons from (125)I decay (approximately 30 keV) delivered at doses rates of 0.19, 0.47, 0.91 and 1.9 mGy/min. The results indicate that at dose rates of 1.9 and 0.91 mGy/min the slope of the induction curve is about 1.5 times less than that measured at high dose rate in previous studies with a similar quality of radiation (28 kVp mammographic energy X rays). In the dose region of 0 to 100 mGy, the data were equally well fitted by a threshold or linear no-threshold model. At dose rates of 0.19 and 0.47 mGy/min there was no induction of transformation even at doses up to 1000 mGy, and there was evidence for a possible suppressive effect. These results show that for this in vitro end point the DDREF is very dependent on dose rate and at very low doses and dose rates approaches infinity. The relative risks for the in vitro data compare well with those from epidemiological studies of breast cancer induction by low- and high-dose-rate radiation.     

Analysis of mortality among Canadian nuclear power industry workers after chronic low-dose exposure to ionizing radiation

Studies of radiation-associated risks among workers chronically exposed to low doses of radiation are important, both to estimate risks directly and to assess the adequacy of extrapolations of risk estimates from high-dose studies. This paper presents results based on a cohort of 45,468 nuclear power industry workers from the Canadian National Dose Registry monitored for more than 1 year for chronic low-dose whole-body ionizing radiation exposures sometime between 1957 and 1994 (mean duration of monitoring = 7.4 years, mean cumulative equivalent dose = 13.5 mSv). The excess relative risks for leukemia [excluding chronic lymphocytic leukemia (CLL)] and for all solid cancers were 52.5 [95% confidence interval (CI): 0.205, 291] and 2.80 (95% CI: -0.038, 7.13) per sievert, respectively, both associations having P values close to 0.05. Relative risks by dose categories increased monotonically for leukemia excluding CLL but were less consistent for all solid cancers combined. Although the point estimates are higher than those found in other studies of whole-body irradiation, the difference could well be due to chance. Further follow-up of this cohort or the combination of results from multiple worker studies will produce more stable estimates and thus complement the risk estimates from higher-dose studies.     

Cancer mortality risk among workers at the Mayak nuclear complex

At present, direct data on risk from protracted or fractionated radiation exposure at low dose rates have been limited largely to studies of populations exposed to low cumulative doses with resulting low statistical power. We evaluated the cancer risks associated with protracted exposure to external whole-body gamma radiation at high cumulative doses (the average dose is 0.8 Gy and the highest doses exceed 10 Gy) in Russian nuclear workers. Cancer deaths in a cohort of about 21,500 nuclear workers who began working at the Mayak complex between 1948 and 1972 were ascertained from death certificates and autopsy reports with follow-up through December 1997. Excess relative risk models were used to estimate solid cancer and leukemia risks associated with external gamma-radiation dose with adjustment for effects of plutonium exposures. Both solid cancer and leukemia death rates increased significantly with increasing gamma-ray dose (P < 0.001). Under a linear dose-response model, the excess relative risk for lung, liver and skeletal cancers as a group (668 deaths) adjusted for plutonium exposure is 0.30 per gray (P < 0.001) and 0.08 per gray (P < 0.001) for all other solid cancers (1062 deaths). The solid cancer dose-response functions appear to be nonlinear, with the excess risk estimates at doses of less than 3 Gy being about twice those predicted by the linear model. Plutonium exposure was associated with increased risks both for lung, liver and skeletal cancers (the sites of primary plutonium deposition) and for other solid cancers as a group. A significant dose response, with no indication of plutonium exposure effects, was found for leukemia. Excess risks for leukemia exhibited a significant dependence on the time since the dose was received. For doses received within 3 to 5 years of death the excess relative risk per gray was estimated to be about 7 (P < 0.001), but this risk was only 0.45 (P = 0.02) for doses received 5 to 45 years prior to death. External gamma-ray exposures significantly increased risks of both solid cancers and leukemia in this large cohort of men and women with occupational radiation exposures. Risks at doses of less than 1 Gy may be slightly lower than those seen for doses arising from acute exposures in the atomic bomb survivors. As dose estimates for the Mayak workers are improved, it should be possible to obtain more precise estimates of solid cancer and leukemia risks from protracted external radiation exposure in this cohort.     

Sensitivity of germ cells and embryos to ionizing radiation

Experiments performed in laboratory animals suggest that ionizing radiation can induce DNA damage in the germ cells of exposed individuals and lead to various deleterious effects in their progeny, including miscarriage, low birth weight, congenital abnormalities and perhaps cancer. However, no clear evidence for such effects has been found in epidemiological studies of people exposed to radiation. The predicted risks of hereditary effects of any kinds resulting from parental exposure to relatively low doses of ionizing radiation remain very low, compared to the spontaneous risks in the absence of irradiation. Irradiation of the mouse embryo can lead to various effects (lethality, growth retardation, congenital abnormalities), depending on the period of gestation at which irradiation occurs. In humans, prenatal irradiation has only been exceptionally associated with congenital abnormalities, but irradiation between weeks 8-25 has been shown to be able to induce severe mental retardation. Although being not proven, the risk of developing a childhood cancer following prenatal irradiation may also not be excluded. Like for genetic effects, the risk of adverse effects following exposure of the embryo to relatively low doses remains quite low compared to the natural risks.     

Investigation on circular asymmetry of geographical distribution in cancer mortality of Hiroshima atomic bomb survivors based on risk maps: analysis of spatial survival data

While there is a considerable number of studies on the relationship between the risk of disease or death and direct exposure from the atomic bomb in Hiroshima, the risk for indirect exposure caused by residual radioactivity has not yet been fully evaluated. One of the reasons is that risk assessments have utilized estimated radiation doses, but that it is difficult to estimate indirect exposure. To evaluate risks for other causes, including indirect radiation exposure, as well as direct exposure, a statistical method is described here that evaluates risk with respect to individual location at the time of atomic bomb exposure instead of radiation dose. In addition, it is also considered to split the risks into separate risks due to direct exposure and other causes using radiation dose. The proposed method is applied to a cohort study of Hiroshima atomic bomb survivors. The resultant contour map suggests that the region west to the hypocenter has a higher risk compared to other areas. This in turn suggests that there exists an impact on risk that cannot be explained by direct exposure.     

Epidemiological studies of cataract risk at low to moderate radiation doses: (not) seeing is believing

The prevailing belief for some decades has been that human radiation-related cataract occurs only after relatively high doses; for instance, the ICRP estimates that brief exposures of at least 0.5-2 Sv are required to cause detectable lens opacities and 5 Sv for vision-impairing cataracts. For protracted exposures, the ICRP estimates the corresponding dose thresholds as 5 Sv and 8 Sv, respectively. However, several studies, especially in the last decade, indicate that radiation-associated opacities occur at much lower doses. Several studies suggest that medical or environmental radiation exposure to the lens confers risk of opacities at doses well under 1 Sv. Among Japanese A-bomb survivors, risks for cataracts necessitating lens surgery were seen at doses under 1 Gy. The confidence interval on the A-bomb dose threshold for cataract surgery prevalence indicated that the data are compatible with a dose threshold ranging from none up to only 0.8 Gy, similar to the dose threshold for minor opacities seen among Chernobyl clean-up workers with primarily protracted exposures. Findings from various studies indicate that radiation risk estimates are probably not due to confounding by other cataract risk factors and that risk is seen after both childhood and adult exposures. The recent data are instigating reassessments of guidelines by various radiation protection bodies regarding permissible levels of radiation to the eye. Among the future epidemiological research directions, the most important research need is for adequate studies of vision-impairing cataract after protracted radiation exposure.     

Cancer mortality following in utero exposure among offspring of female mayak worker cohort members

Little is known about long-term cancer risks following in utero radiation exposure. We evaluated the association between in utero radiation exposure and risk of solid cancer and leukemia mortality among 8,000 offspring, born from 1948-1988, of female workers at the Mayak Nuclear Facility in Ozyorsk, Russia. Mother's cumulative gamma radiation uterine dose during pregnancy served as a surrogate for fetal dose. We used Poisson regression methods to estimate relative risks (RRs) and 95% confidence intervals (CIs) of solid cancer and leukemia mortality associated with in utero radiation exposure and to quantify excess relative risks (ERRs) as a function of dose. Using currently available dosimetry information, 3,226 (40%) offspring were exposed in utero (mean dose = 54.5 mGy). Based on 75 deaths from solid cancers (28 exposed) and 12 (6 exposed) deaths from leukemia, in utero exposure status was not significantly associated with solid cancer: RR = 0.94, 95% CI 0.58 to 1.49; ERR/Gy = -0.1 (95% CI < -0.1 to 4.1), or leukemia mortality; RR = 1.65, 95% CI 0.52 to 5.27; ERR/Gy = -0.8 (95% CI < -0.8 to 46.9). These initial results provide no evidence that low-dose gamma in utero radiation exposure increases solid cancer or leukemia mortality risk, but the data are not inconsistent with such an increase. As the offspring cohort is relatively young, subsequent analyses based on larger case numbers are expected to provide more precise estimates of adult cancer mortality risk following in utero exposure to ionizing radiation.     

Radiation Protection in Canada: Part VII. Setting Standards for Radiation Protection

The current recommendations of the International Commission on Radiological Protection have as a basic objective the limitation of the radiation dose to “that which involves a risk that is not unacceptable to the individual and to the population at large”. The problem is to decide what degree of risk is acceptable, in relation to the benefits of a practice that necessitates a radiation exposure. At the present time it is not possible to make more than very rough estimates of some of the risks of exposure to radiation, but such estimates can be usefully compared with some of the other risks that are tolerated by society. On the assumption that it would be possible to make quantitative assessments of both the benefits and the risks, the question is raised as to how and by whom an appropriate balance should be made.     

Mortality from solid cancers other than lung,liver, and bone in relation to external dose among plutonium and non-plutonium workers in the Mayak Worker Cohort

Exposure to ionizing radiation has well-documented long-term effects on cancer rates and other health outcomes in humans. While in vitro experimental studies had demonstrated that the nature of some radiation effects depend on both total dose of the radiation and the dose rate (i.e., the pattern of dose distribution over time), the question of whether or not the carcinogenic effect of radiation exposure depends on the dose rate remains unanswered. Another issue of interest concerns whether or not concomitant exposure to external gamma rays and inhaled plutonium aerosols has any effect on the external exposure effects. The analyses of the present paper focus on the risk of solid cancers at sites other than lung, liver, and bone in Mayak workers. Recent findings are reviewed indicating that there is no evidence of plutonium dose response for these cancers in the Mayak worker cohort. Then the evidence for differences in the external dose effects among workers with and without the potential for exposure to alpha particles from inhaled plutonium is examined. It is found that there is no evidence that exposure to plutonium aerosols significantly affects the risk associated with external exposure. While the Mayak external dose risk estimate of an excess relative risk of 0.16 per Gy is somewhat lower than an appropriately normalized risk estimate from the Life Span Study of Japanese atomic bomb survivors, the uncertainties in these estimates preclude concluding that the external dose excess relative risks of this group of solid cancers differ in the two cohorts.     

Long-term follow-up for brain tumor development after childhood exposure to ionizing radiation for tinea capitis

Ionizing radiation is an established risk factor for brain tumors, yet quantitative information on the long-term risk of different types of brain tumors is sparse. Our aims were to assess the risk of radiation-induced malignant brain tumors and benign meningiomas after childhood exposure and to investigate the role of potential modifiers of that risk. The study population included 10,834 individuals who were treated for tinea capitis with X rays in the 1950s and two matched nonirradiated groups, comprising population and sibling comparison groups. The mean estimated radiation dose to the brain was 1.5 Gy. Survival analysis using Poisson regression was performed to estimate the excess relative and absolute risks (ERR, EAR) for brain tumors. After a median follow-up of 40 years, an ERR/Gy of 4.63 and 1.98 (95% CI = 2.43-9.12 and 0.73-4.69) and an EAR/Gy per 10(4) PY of 0.48 and 0.31 (95% CI = 0.28-0.73 and 0.12-0.53) were observed for benign meningiomas and malignant brain tumors, respectively. The risk of both types of tumors was positively associated with dose. The estimated ERR/Gy for malignant brain tumors decreased with increasing age at irradiation from 3.56 to 0.47 (P = 0.037), while no trend with age was seen for benign meningiomas. The ERR for both types of tumor remains elevated at 30-plus years after exposure.     

Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases

This is the 14th report in a series of periodic general reports on mortality in the Life Span Study (LSS) cohort of atomic bomb survivors followed by the Radiation Effects Research Foundation to investigate the late health effects of the radiation from the atomic bombs. During the period 1950-2003, 58% of the 86,611 LSS cohort members with DS02 dose estimates have died. The 6 years of additional follow-up since the previous report provide substantially more information at longer periods after radiation exposure (17% more cancer deaths), especially among those under age 10 at exposure (58% more deaths). Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose response, and effect modification by gender, age at exposure, and attained age. The risk of all causes of death was positively associated with radiation dose. Importantly, for solid cancers the additive radiation risk (i.e., excess cancer cases per 10(4) person-years per Gy) continues to increase throughout life with a linear dose-response relationship. The sex-averaged excess relative risk per Gy was 0.42 [95% confidence interval (CI): 0.32, 0.53] for all solid cancer at age 70 years after exposure at age 30 based on a linear model. The risk increased by about 29% per decade decrease in age at exposure (95% CI: 17%, 41%). The estimated lowest dose range with a significant ERR for all solid cancer was 0 to 0.20 Gy, and a formal dose-threshold analysis indicated no threshold; i.e., zero dose was the best estimate of the threshold. The risk of cancer mortality increased significantly for most major sites, including stomach, lung, liver, colon, breast, gallbladder, esophagus, bladder and ovary, whereas rectum, pancreas, uterus, prostate and kidney parenchyma did not have significantly increased risks. An increased risk of non-neoplastic diseases including the circulatory, respiratory and digestive systems was observed, but whether these are causal relationships requires further investigation. There was no evidence of a radiation effect for infectious or external causes of death.     

Evaluation and re-evaluation of genetic radiation hazards in man III. Other relevant data and risk assessment

Some of the advances in mammalian radiation genetics, human genetics and cytogenetics that were made during the last 2–3 years and that have either a direct bearing on, or that may be potentially useful in, the evaluation of genetic radiation hazards in man have been examined. Among these are (1) the new data on the incidence of genetic diseases in man; (2) the latest results of the study of mortality rates among children born to survivors of the atomic bombings of Hiroshima and Nagasaki; (3) new data on the radition-induction of reciprocal translocations in human spermatogonia; (4) new results from radiation studies with mice on skeletal mutations, autosomal recessive lethals, sex-chromosome losses, translocation induction and recovery etc., and (5) a re-analysis of the earlier data on dose-rate effects for the induction of specific locus mutations in mouse spermatogonia. Using the pertinent new information as a basis, quantitative estimates are presented employing both a direct method of expressing risks in terms of effects per unit dose of irradiation and the indirect doubling-dose method of expressing these as increments over the load of genetic disorders occuring spontaneously in man.     

Influence of radiation dose patterns on lung tumor incidence in dogs that inhaled beta emitters: a preliminary report

Different radiation dose patterns to the lung from inhaled beta-emitting radionuclides may influence the frequency and kind of biological effects. To determine the magnitude of this influence, groups of Beagle dogs were exposed to aerosols of 90Y, 91Y, 144Ce, or 90Sr in relatively insoluble particles and observed for their life spans. Different dose patterns were achieved by using these radionuclides having similar beta emissions and chemical form but having physical half-lives ranging from 2.6 days to 28 years. The range of initial lung burdens of radionuclides studied resulted in a range of biological effects from early deaths at the highest radiation doses to no discernible effects at the lowest doses. The effective half-lives of the four radionuclides in the lung ranged from 2.5 to 600 days. Within 1.5 years after exposure, some dogs died with radiation pneumonitis and pulmonary fibrosis. Between 1.5 and 10 years after exposure, 42 pulmonary carcinomas and 28 pulmonary sarcomas were observed in 163 dogs that died. Protracted irradiation of the lung from 90Sr or 144Ce resulted in a relatively high radiation dose and produced more total lung tumors but fewer lung tumors per rad than less protracted irradiation from 90Y or 91Y. At 10 years after inhalation exposure, the difference in risk per rad among the different dose patterns was a factor of 4 to 8, indicating that the different radiation dose patterns from inhaled beta emitters do influence lung tumor risk factors, at least at high (greater than 20,000 rad) doses to lung.     

The Southern Urals radiation studies. A reappraisal of the current status

In the late 1940s and early 1950s the nuclear workers of the Mayak Production Association in the Southern Urals were exposed to high doses from gamma-rays and from incorporated plutonium. In addition, the population of the Techa riverside downstream of the plutonium-production sites received continued exposures from external gamma-rays due to fission products released into the river and from the internal radiation due to incorporation of the fission products. Based on two international coordination meetings in 1998 and 2000, a synopsis has been given recently in this journal of the radioepidemiological studies on these exposed populations. This commentary describes the current status of these singular investigations with regard to the dosimetry, the assessment of late health effects, and the risk estimation both for the Mayak nuclear workers and the Techa riverside population. A central issue are newly published reduced estimates of the external dose to the Techa riverside population which imply substantially increased risk coefficients for solid cancer. Unless the new dosimetry system, TRDS-2000, has missed a major dose contribution, there is now conspicuous disagreement with current risk estimates. Unaccounted doses from atmospheric releases of fission products and from radiological screening of the Techa riverside population need to be explored, but underestimation of the short lived fission products released into the river appears to be a more critical factor. It is furthermore argued that even if TRDS-2000 were confirmed it would remain questionable whether risk estimates can be based on organ-specific doses when they are obtained in a population with a much higher bone-marrow exposure that may possibly have caused an 'abscopal' radiation effect.     

Tumor induction in BALB/c female mice after fission neutron or gamma irradiation

This study was designed to examine the dose-response relationships for tumor induction after neutron irradiation in female BALB/c mice, with emphasis on the response in the dose range 0 to 50 rad. Tumors induced after radiation exposure included ovarian tumors, lung adenocarcinomas, and mammary adenocarcinomas. For comparison the dose responses for induction of these tumors after 137Cs gamma irradiation were also examined. As previously described for the female RFM mouse, the data for ovarian tumor induction after neutron and gamma irradiation were consistent with a threshold model. For lung and mammary tumors the dose-response curve after neutron irradiation appeared to "bend over" in the dose range 10 to 20 rad. The factors responsible for this bend-over and their relative contributions to the overall form of the dose-response relationship are not presently known. However, these data strongly indicate that extrapolation from data above 50 rad could result in a significant underestimate of risks. Further, it is clear that current models of neutron carcinogenesis are inadequate, since such a bend-over is not predicted at these low dose levels.