[Some Aspects of Medical Activities to Overcome Consequences of Chernobyl Accident].

The results of the long term work of the Russian Scientific Centre of Roentgenology and Radiology on me- dical investigation of the participants in the liquidation of the consequences of Chernobyl power plant acci- dent have been summarized. It has been stated that circulatory system and tumor diseases occupy the leading position in the disease rate among the affected liquidators. The important role of cytogenetic investigation was pointed out. It allows us not only to determine the efficient impact on the human body but also to evaluate the effective dose of radiation, the information about which allows us to predict the development of distant post-irradiation pathology. The results of cytogenetic investigations testify to the interrelation between the level of chromosomal abnormalities and cardiovascular diseases and confirm the clinical data on the non- neoplastic.pathology among the liquidators of the accident.

A follow-up cytogenetic study of workers highly exposed inside the Chernobyl sarcophagus.

Data are presented on some of the engineers and scientists who regularly entered highly radioactive areas of the sarcophagus chamber constructed around the ruins of the Chernobyl reactor. Previous investigations on six of them by unstable chromosomal aberrations, quartz fibre electrometers and, in some cases, tooth electron spin resonance have all indicated high doses accumulated over several years of work inside the sarcophagus. Here, the authors present the data on eleven of the men who agreed to be monitored cytogenetically although two have since died aged 45 and 66 y. The present data were combined with the previous to examine the time-courses of these individuals' changes in their aberration frequencies. As expected, dicentric aberrations showed a clear drop down to 2-3 per 100 cells since the men ceased working inside the sarcophagus. In contrast, the translocation yields remained at a high level showing no tendency to decrease and so proved reliable for retrospective biodosimetry. These data are particularly useful in demonstrating the value of FISH long after high but protracted and fractionated exposure.

Biological dosimetry in Russian and Italian astronauts.

Large uncertainties are associated with estimates of equivalent dose and cancer risk for crews of long-term space missions. Biological dosimetry in astronauts is emerging as a useful technique to compare predictions based on quality factors and risk coefficients with actual measurements of biological damage in-flight. In the present study, chromosomal aberrations were analyzed in one Italian and eight Russian cosmonauts following missions of different duration on the MIR and the international space station (ISS). We used the technique of fluorescence in situ hybridization (FISH) to visualize translocations in chromosomes 1 and 2. In some cases, an increase in chromosome damage was observed after flight, but no correlation could be found between chromosome damage and flight history, in terms of number of flights at the time of sampling, duration in space and extra-vehicular activity. Blood samples from one of the cosmonauts were exposed in vitro to 6 MeV X-rays both before and after the flight. An enhancement in radiosensitivity induced by the spaceflight was observed.

Chromosome aberration dosimetry in cosmonauts after single or multiple space flights.

BACKGROUND AND AIMS: Cosmic radiation is one of the main hazards for manned space exploration. Uncertainty in radiation risk estimates for crews of long-term missions are very high, and direct biological measurements are necessary. We measured chromosomal aberrations in peripheral blood lymphocytes from 33 cosmonauts involved in space missions during the past 11 years. METHODS: Blood lymphocytes from the cosmonauts were stimulated to grow in vitro and were harvested at their first mitosis. Slides were either stained with Giemsa stain for dicentrics analysis, or painted with whole-chromosome DNA probes for translocation analysis (FISH). RESULTS: A statistically significant increase in the yield of chromosomal aberrations was measured following long-term space missions in lymphocytes from cosmonauts at their first flight. No significant changes in aberration frequencies were observed for short-term taxi flights. The increase in long-term missions was consistent with the values calculated from physical dosimetry data. However, for cosmonauts involved in two or more space flights, the yield of interchromosomal exchanges was not related to the total duration of space sojourn or integral absorbed dose. Indeed, the yield of aberrations at the end of the last mission was generally in the range of background frequencies measured before the first mission. CONCLUSIONS: Chromosome aberration dosimetry can detect radiation damage during space flight, and biological measurements support the current risk estimates for space radiation exposure. However, for cosmonauts involved in multiple space missions the frequency of chromosomal aberrations is lower than expected, suggesting that the effects of repeated space flights on this particular endpoint are not simply additive. Changes in the immune system in microgravity and/or adaptive response to space radiation may explain the apparent increase in radioresistance after multiple space flights.

Cytogenetic studies of blood lymphocytes from cosmonauts after long-term space flights on Mir station.

Long-term space missions may increase risks of unfavorable consequences for cosmonauts as a result of radiation effects. This paper presents results of a study of cytogenetic damage in cosmonauts' peripheral blood lymphocytes induced by space radiation. Cultivation of lymphocytes and analysis of chromosomal aberrations were made according to generally accepted methods. It is shown that the yields of dicentrics and centric rings scored after long-term space flights are considerably higher than those scored prior to the flights. An attempt was made to assess individual doses received by cosmonauts. Individual biodosimetry doses received by cosmonauts who showed a reliable increase in the yields of chromosomal-type aberrations after their first flights were estimated to be from 0.02 to 0.28 Gy.

Collaborative exercise on the use of FISH chromosome painting for retrospective biodosimetry of Mayak nuclear-industrial personnel.

PURPOSE: To investigate within the framework of a multilaboratory study the suitability of FISH chromosome painting to measure so-called stable translocations in peripheral lymphocytes of Mayak nuclear-industrial workers (from the Southern Urals) and their use for retrospective biodosimetry. MATERIALS AND METHODS: Chromosime analyses were carried out from 69 workers who had received protracted occupational radiation exposures (0.012-6.065 Gy) up to approximately 40 years before blood sampling. Twenty-one unexposed people living in the same area were controls. A multicolour FISH-painting protocol with the target chromosomes 1, 4 and 8 simultaneously with a pancentromeric probe was used to score potentially transmissible chromosome-type aberrations (reciprocal translocations 2B and related 'one-way' patterns I-III according to the S&S classification). RESULTS: Individual biodosimetry estimates were obtained in terms of these potentially long-term surviving aberration types based on the linear component of a low dose-rate gamma-ray calibration curve produced using identical staining and scoring protocols. For comparison, the workers personal and total background doses were converted to red bone marrow doses. The estimated doses were mainly lower than would be predicted by the calibration curve, particularly at accumulated higher dose levels. CONCLUSIONS: Owing to the limited life-time of circulating T-lymphocytes, the long-term persistence of translocations in vivo requires the assumption of a clonal repopulation of these naturally senescing cells from the haemopoietic stem cell compartments. Obviously such a replacement cannot be fully achieved, leading to a temporal decline even of the yield of transmissible aberrations types. Assuming further a highly selective capacity of stem cells against any type of chromosomal damage and the fact that one must rely on partial genome findings, the potential of FISH chromosome painting for retrospective dose reconstruction is probably limited to a decade or so after high-level protracted radiation exposure.

Analysis of symmetrical translocations for retrospective biodosimetry in radiation workers of the Mayak nuclear-industrial complex (Southern Urals) using FISH-chromosome painting.

PURPOSE: Frequencies of symmetrical translocations were determined by fluorescence in situ hybridization (FISH) for retrospective biodosimetry in workers occupationally exposed to external gamma-rays and internal plutonium at the Mayak nuclear-industrial complex (Southern Urals, Russia). MATERIALS AND METHODS: Chromosome analyses were carried out on peripheral lymphocytes from 75 Mayak workers who had received their main exposures between 1948 and 1963. Cumulative external gamma-ray doses between 0.02 and 9.91 Sv and plutonium burdens ranging between 0.26 and 18.5 kBq are reported. As controls, 33 unexposed persons from non-contaminated areas of the Southern Urals were used. Whole-chromosome painting probes for chromosomes 1, 4 and 12 were used simultaneously with a pancentromeric probe. RESULTS: Compared with the control group, a significantly elevated translocation frequency was found for the total study group and for either of two subsets with (48 subjects) and without (27 subjects) plutonium incorporation. The dicentric frequency was not significantly different from the control level. In the pooled data set, translocation frequencies showed a significant dependence on cumulative external gamma-ray doses. Plutonium uptake had no substantial influence. Individual dose estimates for 21 cases exhibiting at least five translocations ranged between 0.5 and 1.8 Gy, which is substantially lower than the workers' registered personal doses. CONCLUSION: At 35-40 years after protracted exposure to low-dose rate external gamma-rays, the postulated lifetime stability of translocations cannot be confirmed. Apparently, the natural loss of translocation-bearing peripheral lymphocytes cannot be fully compensated so that a temporal decline even of transmissible aberrations takes place. As a consequence, individual retrospective biodosimetry estimates cannot be obtained reliably from the remaining fraction of translocations.

FISH-based analysis of stable translocations in a Techa River population.

PURPOSE: Measurements of symmetrical translocations by fluorescence in situ hybridization (FISH) were performed for retrospective biodosimetry in a Techa River population exposed to external (gamma-rays) and internal (90Sr, 137Cs) irradiation. MATERIALS AND METHODS: Chromosome analyses were carried out on peripheral lymphocytes from 73 radiation-exposed residents from settlements along the Techa River (Southern Urals, Russia) located 7-148 km downstream from the site of release of liquid radioactive waste from the plutonium production facility Mayak. Thirty-nine unexposed persons from non-contaminated areas were used as controls. Whole-chromosome painting probes for chromosomes 1, 4 and 12 were used simultaneously with a pancentromeric probe. RESULTS: A significantly elevated mean translocation frequency compared with controls was found for the total study group and for either of two subgroups of inhabitants residing in villages of the upper regions of the Techa River (7-60 km) during 1950 to 1951, or in villages of the lower regions (78-148 km) until the time of blood sampling. Within the first subgroup, subjects born between 1937 and 1949 showed higher translocation frequencies than those born between 1914 and 1936. Collective biodosimetry estimates for the various groups were between 0.24 and 0.54 Gy. Individual dose estimates for seven subjects with at least five translocations ranged between 0.77 and 1.80 Gy and compared well with doses reconstructed on the basis of 90Sr whole-body counts (WBC) and electronic paramagnetic resonance (EPR) measurements. Individual translocation frequencies from 40 subjects with existing WBC data and calculated cumulative red bone marrow doses below 0.6 Gy fall within the 95% prediction limits of the calibration curve. CONCLUSIONS: FISH-based translocation measurements can provide useful information for a retrospective biodosimetric interpretation. However, with the analysed number of cells, individual estimates required for a reliable evaluation of this highly variable exposure situation can be obtained only for a minority of subjects. In addition, influence of a temporal decline on the yield of stable translocations cannot be fully excluded.

Retrospective biodosimetry of Chernobyl clean-up workers using chromosome painting and conventional chromosome analysis.

Blood samples of 52 Chernobyl clean-up workers were analysed by fluorescence in situ hybridization (FISH) using whole-chromosome painting probes for chromosomes 1, 4 and 12, simultaneously with a pancentromeric probe and by conventional chromosome analysis, for radiation-induced symmetrical translocations and dicentrics in T-lymphocytes. Based on FISH measurements of translocations, individual biodosimetry estimates between 0.32 and 1.0 Gy were obtained from 18 cases. Pooled data for the total group of 52 workers provided a collective biodosimetry estimate of 0.23 Gy. For a group of 34 workers with documented doses, the mean dose estimate of 0.25 Gy compared well with the mean documented dose of 0.26 Gy. However, no correlation between individual translocation frequencies (FG) and documented doses could be found. A statistical analysis of the expected dose-response suggests exposures to higher doses than documented for a substantial fraction of workers with ascribed doses < 0.2 Sv. For subjects working repeatedly at the reactor site between 1986 and 1995 the mean translocation frequency was significantly higher than for those working only in 1986. A comparison of dicentric frequencies obtained by conventional scoring and by FISH measurements showed no significant difference, although only two of 52 cases revealed significantly higher yields than the mean control level. Based on conventionally scored dicentric frequencies, a collective biodosimetry estimate of 0.23 Gy could be derived only of the group of persons working at Chernobyl exclusively in 1986 for which a documented average dose of 0.19 Gy was reported.