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Frequency of lymphocytes mutant at T-cell receptor (TCR) loci was defined in 42 workers of nuclear chemical plants. In 11 persons mainly exposed to external radiation the mean frequency of TCR-mutant lymphocytes was statistically significant by higher compared with control group of unexposed donors: 9.1 x 10(-4) vs 3.5 x 10(-4) correspondently (p < 0.01). Frequency of TCR-mutant lymphocytes did not correlate neither the frequency of structural mutations non doses of external exposure. In group of workers exposed to combined external and internal radiation (n = 31) the average frequency of TCR-mutant lymphocytes was higher compared with control level: 8.9 x 10(-4) vs 3.5 x 10(-4) correspondently (p < 0.01). Correlations between the frequency of TCR-mutant cells and Pu content in organism (r = 0.5; p = 0.005) and between the frequency of chromosome aberration of unstable and stable types (r = 0.5; p = 0.002 and r = 0.6; p = 0.036, correspondently) were set. Comparison of results of analysis of structural and gene mutations allows us to supose that in case of external exposure the observed disturbances can result from genome instability in remote period after irradiation. In case of combined exposure the genetic changes were possibly caused by the constant action of alpha-radiation from Pu containing in the body.

Suggestions that exposure to intakes of alpha-emitting radionuclides such as plutonium could result in a specific profile of chromosome damage distinguishable from that of low LET irradiation have led to the re-analysis of the different types of chromosome aberrations in peripheral blood lymphocytes determined by G-banding in a group of 20 plutonium workers from the British Nuclear Fuels plc facility at Sellafield, UK. Comparisons were made with a group of workers with negligible plutonium intakes but similar external gamma doses and with an unexposed control group. Examination of simple translocation frequencies in the three groups indicated a significant difference (P = 0.033), with the higher frequency in the plutonium workers indicating that exposure from plutonium was contributing to the aberration yield. Slightly raised frequencies of both intra-chromosomal and complex aberrations were observed in the plutonium workers in comparison with the comparable external exposure group and the control group but the difference did not reach significance at the P = 0.05 level and there was no variation in the relative frequencies of the different aberration types between the three groups. There was, therefore, no firm indication from this study that either intra-chromosomal or complex aberrations could be used as a specific marker of high LET exposure in workers with historical intakes of plutonium.

The article describes a case of slowly soluble plutonium and americium compounds entering human body via skin wound. During the wound healing, the authors followed features of biokinetics of the radioactive substances, determined the major route of their excretion, evaluated efficiency of surgical d-bridement and complexation medicine (pentacin). clinical and biophysicdata collected could serve to increase efficiency of urgent therapeutic and prophylactic measures aimed to individuals with wounds contaminated with radioactive substances.

Bystander effects from ionizing radiation have been detailed for a number of cell systems and a number of end points. We wished to use a cell culture/ex vivo rat model of respiratory tissue to determine whether a bystander effect detected in culture could also be shown in a tissue. Examination by immunofluorescence techniques of tracheal cell cultures after exposure to very low doses of alpha particles revealed a large proportion of cells with proliferating cell nuclear antigen (PCNA) bound in their nuclei. PCNA was selected as an end point because it is involved in both DNA repair and the changes in cell cycle that are typical of many reported bystander effects. Maximum response can be detected in up to 28% of the cells in sub-confluent cultures with a dose of only 2 mGy. At this dose less than 2% of the cell nuclei have experienced a particle traversal and less than 6% of the cells have experienced an alpha-particle traversal through either their nucleus or some part of their cytoplasm. The hypothesis that this bystander response in nontargeted cells is mediated through secreted factor(s) is presented, and supporting evidence was found using partial irradiation and co-culture experiments. Examination of the effect with excised pieces of trachea demonstrated a response similar to that seen in culture.

The cohort of nuclear workers at the Mayak Production Association, located in the Russian Federation, is a unique resource for providing information on the health effects of exposure to plutonium as well as the effects of protracted external dose. Lung cancer mortality risks were evaluated in 21,790 Mayak workers, a much larger group than included in previous evaluations of lung cancer risks in this cohort. These analyses, which included 655 lung cancer deaths occurring in the period 1955-2000, were the first to evaluate both excess relative risk (ERR) and excess absolute risk (EAR) models and to give detailed attention to the modifying effects of gender, attained age and age at hire. Lung cancer risks were found to be significantly related to both internal dose to the lung from plutonium and external dose, and risks were described adequately by linear functions. For internal dose, the ERR per gray for females was about four times higher than that for males, whereas the EAR for females was less than half that for males; the ERR showed a strong decline with attained age, whereas the EAR increased with attained age until about age 65 and then decreased. Parallel analyses of lung cancer mortality risks in Mayak workers and Japanese A-bomb survivors were also conducted. Efforts currently under way to improve both internal and external dose estimates, and to develop data on smoking, should result in more accurate risk estimates in the future.

The authors conducted a nested case-control study of the association between lung cancer mortality and cumulative internal lung doses among a cohort of workers employed at the Rocky Flats Plant in Colorado from 1951 to 1989. Cases (n = 180) were individually matched with controls (n = 720) on age, sex, and birth year. Annual doses to the lung from plutonium, americium, and uranium isotopes were calculated for each worker with an internal dosimetry model. Lung cancer risk was elevated among workers with cumulative internal lung doses of more than 400 mSv in several different analytical models. The dose-response relation was not consistent at high doses. Restricting analysis to those employed for 15-25 years produced a statistically significant linear trend with dose (chi-square = 67.2, p < 0.001), suggesting a strong healthy worker survivor effect. The association between age at first internal lung dose and lung cancer mortality was statistically significant (odds ratio = 1.05, 95% confidence interval: 1.01, 1.10). No associations were found between lung cancer mortality and cumulative external penetrating radiation dose or cumulative exposures to asbestos, beryllium, hexavalent chromium, or nickel.

The examinees demonstrated definite effects caused by total influence of Am-241 and Pu-239: chronic radiation sickness with diffuse pneumosclerosis, chronic toxic radiation bronchitis and peripheral blood changes (reactive alterations and stable lower platelets and reticulocytes count), microfocal hypoplasia, osteodysplasia, reactive hepatopathy. Frequency of these effects increased with higher radiation exposure and did not depend on the age.

Berylliosis and plutonium pneumosclerosis patients appeared to have two types of pulmonary hypertension: hypervolemic and hypertonic ones. Hypervolemic type of pulmonary circulation was revealed in 31.7% of berylliosis patients and in 53.8% of plutonium pneumosclerosis patients. Hypertonic type of pulmonary circulation was seen in 68.3% of berylliosis patients and in 46.2% of plutonium pneumosclerosis patients mainly at stages II and III. Berylliosis and plutonium pneumosclerosis patients are subjects for early pulmonary hypertension--moderate in most patients at stage I and high at stage II and III. Pulmonary hypertension is a main pathogenetic factor underlying chronic corpulmonale formation.

This paper briefly reviews the contributions made by human tissue studies to improved understanding of the biokinetics, dosimetry and potential bioeffects of plutonium in man. It includes consideration of tissue donations from both environmental and occupational populations, along with a brief history of human experience with plutonium and consideration of the bioethical aspects of post-mortem human tissue sampling.

Background: Studies of nuclear workers have focused mainly on the experience of male workers. To date, little has been published specifically on the experience of female workers in the nuclear industry., Methods: We report on the mortality, cancer morbidity, and tracing experience of the 6,376 females ever employed at the British Nuclear Fuels Ltd. plant at Sellafield to the end of 1998. These workers have accumulated 142,337 person-years of experience., Results: Radiation workers were exposed to low doses of radiation. No statistically significant associations were noted between mortality or cancer morbidity and cumulative assessed organ-specific internal plutonium dose or cumulative external whole body radiation dose overall, or for any of the individual disease groupings examined. The power of the study was insufficient to detect the risks indicated in other radiation studies., Conclusion: This study offers reassurance that there is no detrimental effect on the health of the female workers from occupational exposures at Sellafield. Am. J. Ind. Med. 44:653-663, 2003., (Copyright 2003 Wiley-Liss, Inc.)

Risk estimates for deterministic effects of inhaled weapons-grade plutonium (WG Pu) are needed to evaluate potential serious harm to (1) U.S. Department of Energy nuclear workers from accidental or other work-place releases of WG Pu; and (2) the public from terrorist actions resulting in the release of WG Pu to the environment. Deterministic health effects (the most serious radiobiological consequences to humans) can arise when large amounts of WG Pu are taken into the body. Inhalation is considered the most likely route of intake during work-place accidents or during a nuclear terrorism incident releasing WG Pu to the environment. Our current knowledge about radiation-related harm is insufficient for generating precise estimates of risk for a given WG Pu exposure scenario. This relates largely to uncertainties associated with currently available risk and dosimetry models. Thus, rather than generating point estimates of risk, distributions that account for variability/uncertainty are needed to properly characterize potential harm to humans from a given WG Pu exposure scenario. In this manuscript, we generate and summarize risk distributions for deterministic radiation effects in the lungs of nuclear workers from inhaled WG Pu particles (standard isotopic mix). These distributions were developed using NUREG/CR-4214 risk models and time-dependent, dose conversion factor data based on Publication 30 of the International Commission on Radiological Protection. Dose conversion factors based on ICRP Publication 30 are more relevant to deterministic effects than are the dose conversion factors based on ICRP Publication 66, which relate to targets for stochastic effects. Risk distributions that account for NUREG/CR-4214 parameter and model uncertainties were generated using the Monte Carlo method. Risks were evaluated for both lethality (from radiation pneumonitis) and morbidity (due to radiation-induced respiratory dysfunction) and were found to depend strongly on absorbed-dose-rate history (which depends on WG Pu solubility). The results obtained were compared to new data from animal and epidemiological studies. Our findings suggest that NUREG/CR-4214 models for assessing lethality risk from inhaled radionuclides may need some modest revision in light the new data. However, for assessing morbidity risks, major revisions may be needed.

A new analysis of lung cancer mortality in a cohort of male Mayak workers who started their employment in the plutonium and reprocessing plants between 1948 and 1958 has been carried out in terms of a relative risk model. The follow-up has been extended until 1999, moreover a new dosimetry system (DOSES2000) has been established. Particular emphasis has been given to a discrimination of the effects of external gamma-exposure and internal alpha-exposure due to incorporated plutonium. This study has also utilized and incorporated the information from a cohort of Mayak reactor workers, who were exposed only externally to gamma-rays. The influence of smoking as the main confounding factor for lung cancer has been studied. The baseline lung cancer mortality rate was not taken from national statistics but was derived from the cohort itself. The estimated excess relative risk for the plutonium alpha-rays was 0.23/Sv (95%CI: 0.16-0.31). The resulting risk coefficient for external gamma-ray exposure was very low with a statistically insignificant estimate of 0.058/Sv (95%CI: -0.072-0.20). The inferred relative risk for smokers was 16.5 (95%CI: 12.6-20.5).

Speculation has long surrounded the question of whether past exposure to ionizing radiation leaves a unique permanent signature in the genome. Intrachromosomal rearrangements or deletions are produced much more efficiently by densely ionizing radiation than by chemical mutagens, x-rays, or endogenous aging processes. Until recently, such stable intrachromosomal aberrations have been very hard to detect, but a new chromosome band painting technique has made their detection practical. We report the detection and quantification of stable intrachromosomal aberrations in lymphocytes of healthy former nuclear-weapons workers who were exposed to plutonium many years ago. Even many years after occupational exposure, more than half the blood cells of the healthy plutonium workers contain large (>6 Mb) intrachromosomal rearrangements. The yield of these aberrations was highly correlated with plutonium dose to the bone marrow. The control groups contained very few such intrachromosomal aberrations. Quantification of this large-scale chromosomal damage in human populations exposed many years earlier will lead to new insights into the mechanisms and risks of cytogenetic damage.

Purpose: To compare quantitative estimates of lifetime cancer risk in humans for exposures to internally deposited radionuclides and external radiation. To assess the possibility that risks from radionuclide exposures may be underestimated., Materials and Methods: Risk estimates following internal exposures can be made for a small number of alpha-particle-emitting nuclides. (1) Lung cancer in underground miners exposed by inhalation to radon-222 gas and its short-lived progeny. Studies of residential (222)Rn exposure are generally consistent with predictions from the miner studies. (2) Liver cancer and leukaemia in patients given intravascular injections of Thorotrast, a thorium-232 oxide preparation that concentrates in liver, spleen and bone marrow. (3) Bone cancer in patients given injections of radium-224, and in workers exposed occupationally to (226)Ra and (228)Ra, mainly by ingestion. (4) Lung cancer in Mayak workers exposed to plutonium-239, mainly by inhalation. Liver and bone cancers were also seen, but the dosimetry is not yet sufficiently good enough to provide quantitative estimates of risks. Comparisons can be made between risk estimates for radiation-induced cancer derived for radionuclide exposure and those derived for the A-bomb survivors, exposed mainly to low-LET (linear energy transfer) external radiation. Data from animal studies, using dogs and rodents, allow comparisons of cancer induction by a range of alpha- and beta-/gamma-emitting radionuclides. They provide information on relative biological effectiveness (RBE), dose-response relationships, dose-rate effects and the location of target cells for different malignancies., Results: For lung and liver cancer, the estimated values of risk per Sv for internal exposure, assuming an RBE for alpha-particles of 20, are reasonably consistent with estimates for external exposure to low-LET radiation. This also applies to bone cancer when risk is calculated on the basis of average bone dose, but consideration of dose to target cells on bone surfaces suggests a low RBE for alpha-particles. Similarly, for leukaemia, the comparison of risks from alpha-irradiation ((232)Th and progeny) and external radiation suggest a low alpha RBE; this conclusion is supported by animal data. Risk estimates for internal exposure are dependent on the assumptions made in calculating dose. Account is taken of the distribution of radionuclides within tissues and the distribution of target cells for cancer induction. For the lungs and liver, the available human and animal data provide support for current assumptions. However, for bone cancer and leukaemia, it may be that changes are required. Bone cancer risk may be best assessed by calculating dose to a 50 micro m layer of marrow adjacent to endosteal (inner) bone surfaces rather than to a single 10 micro m cell layer as currently assumed. Target cells for leukaemia may be concentrated towards the centre of marrow cavities so that the risk of leukaemia from bone-seeking radionuclides, particularly alpha emitters, may be overestimated by the current assumption of uniform distribution of target cells throughout red bone marrow., Conclusions: The lifetime risk estimates considered here for exposure to internally deposited radionuclides and to external radiation are subject to uncertainties, arising from the dosimetric assumptions made, from the quality of cancer incidence and mortality data and from aspects of risk modelling; including variations in baseline rates between populations for some cancer types. Bearing in mind such uncertainties, comparisons of risk estimates for internal emitters and external radiation show good agreement for lung and liver cancers. For leukaemia, the available data suggest that the assumption of an alpha-particle RBE of 20 can result in overestimates of risk. For bone cancer, it also appears that current assumptions will overestimate risks from alpha-particle-emitting nuclides, particularly at low doses.

Chronic exposure to high LET radiation has been shown to cause liver cancer in humans based on studies of patients who received Thorotrast, a colloidal suspension of thorium dioxide formerly used as a radiological contrast agent, and on studies of Russian nuclear weapons workers exposed to internally ingested plutonium. Risk estimates for these exposures and specific subtypes of liver cancer have not been previously reported. Combining published data with tumor registry data pertinent to the Thorotrast cohorts in Germany, Denmark, Portugal, and Japan and to Russian workers, we generally found significantly elevated risks of three major histologic types of liver tumors: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and hemangiosarcoma (HS) for Thorotrast exposures. In contrast, HS was the only liver tumor significantly associated with the lower alpha-particle doses experienced by the Russian workers. Excess cases per 1,000 persons exposed to Thorotrast were similar for the three liver cancer subtypes but lower for plutonium exposure. Odds ratios (OR) of HS and CC for Thorotrast were from 26 to 789 and from 1 to 31 times higher than those for HCC, respectively. ORs of liver cirrhosis for Thorotrast exposure ranged from 2.7 (95% confidence interval (CI): 2.2-3.4) to 6.7 (5.1-8.7).

For radiation-related cancer risk evaluation, it is important to assess not only influences of individual risk factors but also their interactive effects (e.g., additive, multiplicative, etc.). Multivariate analysis methods adapted for interactive effects allow such assessments. We have used a multivariate analysis approach to investigate the pair-wise interactions of the previously identified three main etiological factors for lung cancer induction in Russian workers of the Mayak Production Association (PA) nuclear enterprise. These three factors are as follows: (1) body burden of inhaled plutonium-239 (239Pu), an influence on absorbed alpha-radiation dose; (2) cumulative, absorbed external gamma-radiation dose to the lung; and (3) level of cigarette smoking as indicated by a smoking index (SI). The SI represents the cigarettes smoked per day times years smoking. The Mayak PA workers were exposed by inhalation to both soluble and insoluble forms of 239Pu. Based on a cohort of 4,390 persons (77% male), we conducted a nested, case-control study of lung cancer induction using 486 matched cases and controls. Each case was matched to two controls. Matching was based on five factors: sex, year of birth, year work began, profession, and workplace. Three levels of smoking were considered: low (SI = 1 to 499), used as a reference level; middle (SI = 500 to 900); and high (SI = 901 to 2,000). For lung cancer induction, a supra-multiplicative effect was demonstrated for high external gamma-ray doses (> 2.0 Gy) plus high 239Pu intakes (body burden >2.3 kBq). This observation is consistent with the hypothesis of curvilinear dose-response relationships for lung cancer induction by high- and low-LET radiations. The interaction between radiation (external gamma rays or 239Pu body burden) and cigarette smoke was found to depend on the smoking level. For the middle level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with additive effects. However, for the high level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with the occurrence of multiplicative effects. These results indicate that low-dose risk estimates for radiation-induced lung cancer derived without adjusting for the influence of cigarette smoking could be greatly overestimated. Further, such systematic error may considerably distort the shape of the risk vs. dose curve and could possibly obscure the presence of a dose threshold for radiation-induced lung cancer.

(137)Cs contamination in living or agricultural environments may contribute to significant human internal exposure and cause adverse health effects. Contamination by (137)Cs and other radionuclides was detected in a river valley in northern Taiwan, in the 1990s. Given that the radioactivity appeared to be widely distributed in soil, rice and several other food plants in the areas surrounding several communities in the late 1990s [Y.B. Nabyvanents, T.F. Gesell, M.H. Jen, W.P. Chang, Distribution of (137)Cs in soil along Ta-han River Valley in Tau-Yuan County in Taiwan, J. Environ. Radioact. 54 (2001) 391], its possible impact on local occupants was further studied. Ten subjects in three families residing continuously in the highly contaminated valley and 10 non-exposed subjects matched for age, sex, and cigarette smoking habits from neighboring communities were evaluated for micronucleus frequencies and for degenerative nuclear changes in urinary exfoliated epithelial cells (EE cells). Micronucleus frequencies ( per thousand ) were significantly higher in the exposed subjects (4.79+/-1.21 per thousand ) than in the reference subjects (2.73+/-0.59 per thousand; Wilcoxon 2-sample test, P value 0.0004). There were also higher frequencies of EE cells with karyolysis and condensed chromatin in the exposed subjects than in reference subjects. These results indicate that genotoxic and/or mutagenic effects on urinary epithelial cells occur in human subjects who have resided for a long time in a radioactively contaminated environment.

This paper summarizes the methods and results of estimating risks of cancer incidence resulting from plutonium, carbon tetrachloride, and beryllium releases from operations at the Rocky Flats Environmental Technology Site, near Denver, Colorado, from 1953 through 1989. The key findings show that people who lived near the facility were exposed to plutonium mainly through inhalation during routine operations, from a major fire in 1957, and from plutonium resuspended from contaminated soil from an outdoor drum storage area, called the 903 Area. Results were presented for five exposure scenarios that were location-independent. Individuals described by the laborer scenario received the highest risk of all scenarios considered. Upper bound (95th percentile) incremental lifetime cancer incidence risks for the laborer scenario were in about the 10(-4) range (1 chance in 10,000) for developing cancer from Rocky Flats plutonium releases during a lifetime. At the 5th percentile level, the maximum cancer risk was about 10(-7) (1 chance in 10 million) for developing cancer during a lifetime. Estimated cancer risks at the 95th percentile level are within the range of for acceptable risks established by the US Environmental Protection Agency of 10(-6) to 10(-4). Carbon tetrachloride was found to be the chemical that presented the highest risk to the public. The 5th and 95th percentile risk values for exposure to carbon tetrachloride were 9.2x10(-7) and 2.5x10(-5), respectively.

The concentrations of 239+240Pu and 137Cs in zooplankton and nekton in the Northwest Pacific and Southern Oceans were measured during the period 1993-1996. The object of the sampling was to assess the potential impacts of existing submerged anthropogenic-radioactive materials in the western North Pacific as well as the East China Sea. Samples from the Bransfield Strait of the Antarctic Ocean provided a control source impacted by only atmospheric bomb fallout. No particularly elevated levels of 239+240Pu were found in zooplankton samples from the Northwest Pacific, although significantly lower levels of 239+240Pu were found in three mixed zooplankton samples from the Bransfield Strait. The body burden of 239+240Pu in zooplankton appears to reflect concentrations in ambient seawater with some variation. Some additional measurements of 137Cs in fish are also reported here to complement existing databases and for future reference in the regional marine environmental radioactivity monitoring effort.

Spectrometry was used by means of an alpha-radiometer on a [symbol: see text]porpecc-[symbol: see text] hard-and-software complex to study the radioactive contamination of the surfaces of neutralizers with plutonium 239-based ionizing radiation sources, which are employed to remove electrical charges from electrifiable materials. While using the neutralizers, the operating personnel is shown to be exposed to radiation. The level of removed radioactive contamination during half-a-year exploitation of the neutralizers was greater than the maximum allowable values on the average by several times. Radiation hazard in the use of radioisotopic neutralizers of static electricity is outlined.

The possible use of radioactivity dispersal devices by terrorist groups has been recently reported in the news. In this paper, we discuss the threat of terrorist attacks by plutonium, with particular attention to the dispersal of plutonium by explosion or fire. Doses resulting from inhalation of radioactive aerosol induced by a plutonium explosion or fire are simulated using a Gaussian plume model (the HOTSPOT code) for different meteorological conditions. Ground contamination and resuspension of dust are also considered in the simulations. Our simulations suggest that acute effects from a plutonium dispersal attack are very unlikely. For late stochastic effects, the explosion poses a greater hazard than fire. However, even in the worst-case scenario, the dispersed plutonium would cause relatively few excess cancers (around 80 in a city of 2 million inhabitants) after many years from the explosion, and these excess cancers would remain undetected against the background of cancer fatalities.

The paper presents results on Pu, U and Th isotope activity concentration measurements in some mushroom samples collected in Poland, Spain and Ukraine. The sampling sites differ a lot with regard to observed levels of Pu, its origin and isotope ratios as well as the environmental properties. Some of the Polish samples were collected in the northeastern part of the country with up to 30 Bq/m2 of Chernobyl Pu deposition. Other Polish and the Spanish samples are from areas with almost exclusively global fallout Pu present. Ukrainian samples were collected in a highly contaminated area with a deposition of about 3.7 kBq/m2 of Chernobyl (239-240)Pu. The maximum (239+240)Pu activity concentration was found equal to (54+/-4) Bq/kg (dw--dry weight) for a Ukrainian Cantharellus cibarius sample. Ukrainian samples have an extremely high radiocesium level, with maximum of (51+/-4) MBq/kg (dw). The maximum (239+240)Pu activity concentration for Polish samples was (81+/-5) mBq/kg (dw) for Xerocomus badius. From the isotopic ratio in this sample it can be concluded that Chernobyl fallout is the origin of Pu. More than twice as large was the Spanish maximum for Hebeloma cylindrosporum but with only global fallout Pu. Some aspects of the transfer of nuclides to fruit bodies is discussed and in some cases the transfer factors or aggregation coefficients were calculated. Especially high transfer factors were found for Hebeloma cylindrosporum from Spain.

We briefly outline existing information about several cohorts in the Southern Urals, Semipalatinsk and the Altai regions, in addition to those discussed in the companion papers in this issue of Radiation and Environmental Biophysics. These include: (a) the East-Urals Radiation Trace (EURT) cohort of individuals (exposed to fallout from the September 1957 explosion of a storage tank containing liquid radioactive waste from the Mayak Production Association) as well as their offspring, (b) the cohort of exposed parents (i.e. workers of the Mayak facility) and their children, having been established with the aim of examining reproductive health, and (c) several additional cohorts in the Altai region and in Semipalatinsk, where investment of additional resources would greatly facilitate the progress of ongoing studies. Furthermore, we include a brief description of the Russian Human Radiobiology Tissue Repository, which has been established in the city of Ozyorsk and is in the process of making an inventory of autopsied tissues from 700 deceased Mayak workers and of collecting and storing donations of blood and tumor tissues from the members of the Mayak workers cohort currently residing in the city.

A model was developed to calculate ambient air concentrations, surface deposition, and lifetime carcinogenic risk with uncertainty from plutonium released to the air from the Rocky Flats Plant between the years 1953 and 1989. The model integrated airborne release estimates and atmospheric dispersion and deposition calculations from 37 years of routine plant operations and episodic releases. Episodic releases included two major fires in 1957 and 1969 that breached the building air filtration systems, and suspension of plutonium contaminated soil from the former 903 waste storage area during high winds. Predicted air concentrations included contributions from site releases and resuspension from contaminated soil. Inhalation was the only exposure pathway considered. Environmental measurements suitable for model validation were lacking for the period when major site releases occurred (1953 to 1970). However, environmental media, such as soil and lake sediment, are natural accumulators and provided evidence of past offsite releases. The geometric mean predicted-to-observed (P/O) ratio for soil was 0.93 with a geometric standard deviation of 1.6. The model systematically underpredicted concentrations near the 903 Area because large, nonrespirable particles that deposited close to the source were not included in release estimates. Plutonium soil inventories for the model domain had P/O ratios ranging from 0.22 to 4.2. The geometric mean P/O ratio for ambient air was 0.90 with a geometric standard deviation of 2.6. Age-dated sediment cores from Standley Lake had a geometric mean P/O ratio of 1.0 with a geometric standard deviation of 1.7. Predicted-to-observed ratios for plutonium inventories in Great Western Reservoir ranged from 0.36 to 1.7. Lifetime cancer incidence risks were calculated for a male laborer scenario who resided in the model domain for the entire assessment time. Maximum cancer risks ranged from 10-6 (5th percentile) to 10(-4) (95th percentile). Most of the exposure was incurred during the 1950's.

Radiation-induced lung cancer risk is currently estimated based on epidemiological data from populations exposed either to relatively uniform, low-LET radiation, or from uranium miners who inhaled radon and its progeny. Inhaled alpha-emitting radionuclides (e.g. Pu and Am) produce distinctive dose patterns that may not be adequately modelled at present. Thus the distribution of Pu is being measured in formalin-fixed autopsy lung tissue from former workers at the Mayak Production Association, and which is maintained in a tissue archive at SUBI. Lungs are sampled using contemporary stereological techniques and Pu particle activities and locations are determined using quantitative autoradiography and morphological identification of lung structures. To date, > 80% of Pu particles have been observed in parenchymal lung tissues with higher concentrations being found in scar tissue. Concentrations of Pu particles in conducting airways are uniformly low, thus indicating that long-term-retained Pu particles are non-uniformly distributed in human lung, mostly in the parenchyma.

The radiation dose due to internal exposures from 239Pu is mainly estimated by measuring actual urinary or faecal excretion of activity and comparing those values with the standard excretion rates calculated from the models of the International Commission on Radiological Protection (ICRP). Recently, on the other hand, uncertainties in the ICRP's models and parameters are under consideration because of the paucity of human data. In addition, there is a possibility of variation between individuals. A code has been developed to reproduce the ICRP's dose coefficients and excretion rates for 239Pu, which is one of the most important elements for occupational exposure. By using this code, the respective transfer rates for the ICRP Publication 67 biokinetic model were modified, and the effect owing to these changes on present hazard assessment was investigated. As a result, it was shown that dose estimates for workers exposed to 239Pu were not very sensitive to changes in these transfer rates.

The availability of cultured lymphocyte preparations from radiation workers with internal deposits of plutonium provided the opportunity to examine whether irradiation of bone marrow cells had induced a transmissible genomic instability manifesting as an increase in de novo chromosome aberrations in descendant cells in the peripheral blood. The men were originally classified as having more than 20% of the maximum permissible body burdens of plutonium, and recent red bone marrow dose calculations provided individual cumulative estimates at the time of sampling ranging up to 1.8 Sv. The initial sampling occurred approximately 10 years after the main major intake, and samples were subsequently taken during three further periods over the following 20 years. Control samples were available from three of the four sampling times. Chromosome analysis of solid Giemsa-stained material revealed no significant differences either in comparisons between the total group of plutonium workers and controls for comparable periods or when the comparisons were restricted to a group of plutonium workers with initial red bone marrow plutonium doses greater than 0.25 Sv. However, the frequencies of cells containing chromatid exchanges, chromatid breaks, and chromosome and chromatid gaps decreased significantly over the study period for both the plutonium workers as a whole and the controls, and a similar fluctuating pattern was seen when sequential samples from groups of the same individuals were examined. Cells with dicentrics, centric rings and excess acentric fragments remained at similar frequencies throughout the study period. There was therefore no evidence from the study of blood lymphocytes for the induction of persistent transmissible genomic instability in the bone marrow of radiation workers with internal deposits of plutonium. The work has, however, confirmed the need for appropriate controls when conducting studies of cytogenetic end points of instability.

G0 human lymphocytes were exposed in vitro to plutonium-239 alpha-particles, with doses ranging from 0 to 1.62 Gy, to provide a dose response curve and to compare complex rearrangements produced by high LET radiation with low LET data from previous work. Metaphase chromosomes 1 and 2 were painted using fluorescence in situ hybridization (FISH) whole chromosome probes. All unstable and stable aberrations involving the painted chromosomes were scored. The whole genome corrected alpha-coefficient for dicentrics was 0.244 +/- 0.023 and for total translocations 0.346 +/- 0.032, when considering simple and complex exchanges. The ratio of bicoloured total translocations to bicoloured dicentrics was 1.21 +/- 0.15 and the ratio of 2-way to 1-way translocations was 1.73 +/- 0.27 for apparently simple exchanges only. A correlation was noted between the distributions of dicentrics and translocations and this applied even when the complex rearrangements were removed. 20% of the observed rearrangements were complex and this observation was independent of dose. Qualitatively, following irradiation with alpha-particles the complex rearrangements observed were of a greater complexity than seen after X- or gamma-rays. Using the Savage and Simpson system to classify the complex rearrangements, the higher order complexes were found to be the most common type observed. However the insertion type increased while the 2F + 2G types decreased when complex rearrangements induced by alpha-particles were compared to those formed after X- or gamma-irradiation.

The risk per unit dose to the four primary cancer sites for plutonium inhalation exposure (lung, liver, bone, bone marrow) is estimated by combining the risk estimates that are derived from four independent approaches. Each approach represents a fundamentally different source of data from which plutonium risk estimates can be derived. These are: (1) epidemiologic studies of workers exposed to plutonium; (2) epidemiologic studies of persons exposed to low-LET radiation combined with a factor for the relative biological effectiveness (RBE) of plutonium alpha particles appropriate for each cancer site of concern; (3) epidemiologic studies of persons exposed to alpha-emitting radionuclides other than plutonium; and (4) controlled studies of animals exposed to plutonium and other alpha-emitting radionuclides extrapolated to humans. This procedure yielded the following organ-specific estimates of the distribution of mortality risk per unit dose from exposure to plutonium expressed as the median estimate with the 5th to 95th percentiles of the distribution in parentheses: lung 0.13 Gy(-1) (0.022-0.53 Gy(-1)); liver 0.057 Gy(-1) (0.011-0.47 Gy(-1)); bone 0.0013 Gy(-1) (0.000060-0.025 Gy(-1)); bone marrow (leukemia), 0.013 Gy(-1) (0.00061-0.05 Gy(-1)). Because the different tissues do not receive the same dose following an inhalation exposure, the mortality risk per unit intake of activity via inhalation of a 1-microm AMAD plutonium aerosol also was determined. To do this, inhalation dose coefficients based on the most recent ICRP models and accounting for input parameter uncertainties were combined with the risk coefficients described above. The following estimates of the distribution of mortality risk per unit intake were determined for a 1-microm AMAD plutonium aerosol with a geometric standard deviation of 2.5: lung 5.3 x 10(-7) Bq(-1) (0.65-35 x 10(-7) Bq(-1)), liver 1.2 x 10(-7) Bq(-1) (0.091-20 x 10(-7) Bq(-1)), bone 0.11 x 10(-7) Bq(-1) (0.0030-4.3 x 10(-7) Bq(-1)), bone marrow (leukemia) 0.049 x 10(-7) Bq(-1) (0.0017-0.59 x 10(-7) Bq(-1)). The cancer mortality risk for all sites was estimated to be 10 x 10(-7) Bq(-1) (2.1-55 x 10(-7) Bq(-1))--a result that agrees very well with other recent estimates. The large uncertainties in the risks per unit intake of activity reflect the combined uncertainty in the dose and risk coefficients.

Purpose: To compare tumour induction in CBA/H mice, principally osteosarcoma and acute myeloid leukaemia, resulting from exposure to the alpha-emitting nuclides, uranium-233, plutonium-239 and americium-241, and to relate differences between the three nuclides to the pattern of dose delivery within tissues., Materials and Methods: Each nuclide was administered intraperitoneally in citrate solution to three groups of adult male CBA/H mice at levels of activity which gave estimated life-time average skeletal doses of about 0.25-0.3 Gy, 0.5-1 Gy and 1-2 Gy. Animals were carefully monitored and sacrificed as soon as they showed signs of ill health; tumours were identified by standard histopathological techniques., Results: Statistical modelling by Cox regression showed that, considering all three nuclides together, there was a highly significant increase in risk of death from osteosarcoma or myeloid leukaemia with increasing dose rate. For osteosarcoma, the effect was significantly greater for 239Pu than 241Am, while separate analysis for 233U showed no significant increase with increasing dose rate. For example, the increase in relative risk of death from osteosarcoma for an increase in life-time average dose rate to bone of 1 mGyd(-1) was 4.2 (2.7-6.5) for 239Pu, 2.3 (1.4-3.4) for 241Am and 1.1 (0.4-3.1) for 233U. For myeloid leukaemia, there was no significant difference between 239Pu and 241Am in the effect of dose rate. The increase in relative risk from myeloid leukaemia for an increase in average dose rate of 1 mGyd(-1) was 1.8 (1.1-2.8) for 239Pu, 2.0 (1.4-2.9) for 241Am and 1.5 (0.8-2.7) for 233U. Significant increases in renal and hepatic carcinomas were also recorded in animals exposed to 233U and 241Am, respectively. Studies of the distribution of the nuclides within the skeleton, published separately, have shown differences in their retention in individual bones and within bone. The proportions of decays occurring near to endosteal bone surfaces and throughout bone marrow were in the order: 239Pu> 241Am>233U., Conclusions: For osteosarcoma, the relative effectiveness of the nuclides in terms of average bone dose, in the order 239Pu>241Am>233U, is consistent with the proportion of dose delivered near to endosteal surfaces. For myeloid leukaemia, the greater effectiveness of 239Pu and 241Am than 233U is consistent with their accumulation in marrow.