The role of cytogenetic examination for prognosis of remote consequences of irradiation

Correlation between the level of somatic pathology and cytogenetic characteristics of blood was analyzed in a group of liquidators of the accident at the Chernobyl Nuclear Power Plant (ChNPP). A statistically significant correlation was found between the occurrence of cardiovascular diseases and the level of chromosome aberrations (total frequency of chromosome aberrations, frequency of dicentrics and centric rings, frequency of chromatid aberrations). The results obtained are of great importance for the substantiated prediction of the development of postradiation pathologies.     

Results of cytogenetic studies of the consequences of the Chernobyl accident

The selected results of the cytogenetic studies of the Chernobyl accident consequences were summarised. The chromosomal aberrations were used as a method of biodosimetry for a dose assessment for victims during the initial period after the Chernobyl accident. A good correlation between doses calculated based on chromosomal aberrations (dicentrics) and severity of acute radiation syndrome observed in clinic was found. The biodosimetry based on conventional cytogenetic technique (dicentrics) has been unsuccessful for various groups (rehabilitation workers, evacuees, inhabitants of contaminated areas) sampled long time after the Chernobyl accident. The possible reasons of the failure are analysed. The original results of multiaberration cell yield observed in different cohorts of the Chernobyl victims are presented. The problems related to the phenomena are discussed.     

The radiation risks of cerebrovascular diseases among the liquidators

The work concerns the assessment of radiation risks for non-cancer diseases of circulatory system among the Chernobyl liquidators. The medical and dosimetric data from Russian National Medical and Dosimetric Registry were used. The cohort data from 1986 to 2000 years of 61017 liquidators are discussed. Radiation risks are established for the cerebrovascular diseases and for the essential hypertension the significant. ERR =0.45/Gy, with 95% CI = (0.11; 0.80) for the cerebrovascular diseases and ERR = 0.36/Gy, with 95% CI = (0.005; 0.71) for the essential hypertension. It approves the results which were established by authors for the similar cohort in 1986-1996. The cerebrovascular diseases (CVD) are considered in greater details. The significant heterogeneity of the radiation risks by working time in Chernobyl zone is shown for the first time. ERR = 0.89/Gy for the working time less then 6 weeks, and ERR = 0.39/Gy in average for all periods of working in the zone. Among the liquidators entered Chernobyl zone during the first year after the accident (29003 liquidators), the CVD's risk group consists of persons accumulated more then 150 mGy from external sources in less, then 6 weeks (RR = 1.18 with 95% CI = (1.00; 1.40)). The significant CVD's risk from averaged dose rate was defined for external doses greater then 150 mGy (ERR for 100 mGy/day = 2.17, with 95% CI = (0.64; 3.69)).     

Elevated frequencies of hypoxanthine phosphoribosyltransferase lymphocyte mutants are detected in Russian liquidators 6 to 10 years after exposure to radiation from the Chernobyl nuclear power plant accident

This study was conducted to determine whether the frequency of hypoxanthine phosphoribosyltransferase (HPRT) deficient lymphocyte mutants would detect an effect of radiation exposure in a population of Russians who were exposed to low levels of radiation while working in 1986 and 1987 as liquidators cleaning up after the Chernobyl nuclear power reactor accident. The HPRT lymphocyte cloning assay was performed on peripheral blood lymphocytes collected between 1992 and 1996 from 142 liquidators and 66 Russian controls, and between 1989 and 1993 from 231 American controls. Russian and American controls were not significantly different for either cloning efficiency or mutant frequency (MF); inclusion of both sets of controls in the analysis increased the ability to detect a Chernobyl exposure effect in the liquidators. After adjusting for age and smoking, the results revealed no significant difference in cloning efficiency of Chernobyl liquidators relative to Russian controls but a significant, 24% increase in liquidator HPRT mutant frequency over Russian controls (90% confidence interval was 7% to 45% increase). The analytical method also accounted for differences in precision of the individual estimates of log CE and log MF and accommodated for outliers. The increase in HPRT mutant frequency of liquidators is an attribute of the exposed population as a whole rather than of individuals. These results demonstrate that, under appropriate circumstances, the HPRT specific locus mutation assay of peripheral blood lymphocytes can be used to detect a semi-acute, low dose radiation exposure of a population, even 6 to 10 years after the exposure.     

Possibilities and limitations of fluorescence in situ hybridization technique in retrospective detection of low dose radiation exposure in post-chernobyl human cohorts

Cytogenetic analysis using the fluorescence in situ hybridisation (FISH) technique was performed late time after the Chernobyl accident in groups of liquidators, evacuees from 30 km exclusive zone, residents of radioactively contaminated areas and control donors age-matched to exposed persons. Stable and unstable chromosome type exchanges were recorded using a hybrid conventional-PAINT nomenclature. The mean yield of stable chromosome exchanges in liquidators did not correlate with registered radiation doses but had a clear negative dependence on the duration of liquidators' staying in Chernobyl zone, that was in a good agreement with early data based on conventional dicentrics plus rings analysis. The overspontaneous excess for stable chromosome exchange level appeared to be higher in evacuees 16-40 years old than that of senior persons, whereas no age-dependent difference occurred for initially induced dicentrics plus rings yields in this cohort. The stable chromosome exchange yield, as well as combined yield of dicentrics plus rings and potentially unstable incomplete translocations in residents of radioactively contaminated areas showed a reasonable positive correlation with levels of 137Cs contamination. The observed yields of stable chromosome exchanges in all three exposed groups appeared to be somewhat lower than those of expected from unstable exchange-based doses which were referred to an in vitro dose response of stable exchanges outcome in human lymphocytes. Thus, FISH analysis can be successfully applied for qualitative cytogenetic indication of past and chronic radiation exposure to low doses but further refinement of FISH-based system for quantitative dose assessment is still required. Some practical approaches of solving this task are discussed.     

Chromosome alterations in cleanup workers sampled years after the Chernobyl accident

Cytogenetic analysis performed 4-13 years after the Chernobyl accident showed an elevated frequency of acentrics, chromatid exchanges, dicentrics and rings in Chernobyl cleanup workers compared to the control group. Cytogenetic data were analyzed according to the information on exposure to radiation (the year when the cleanup workers worked at the Chernobyl station, doses rates, time elapsed since exposure to radiation, and cytogenetic examination) and some lifestyle factors. The data obtained suggested that some types of chromosome aberrations could be influenced by the action of different environmental factors or lifestyle factors. The frequency of acentrics was correlated with the age of the cleanup workers, and the increased chromatid exchange frequency was attributed to smoking. The numbers of dicentrics and rings suggested a genotoxic effect of ionizing radiation that is still present over 13 years after the exposure.     

Results of dynamic cytogenetic study of children and teenagers living in areas, radioactive by contaminated after the Chernobyl accident

Results of multiyear cytogenetic study of children and teenagers living in areas, radioactive by contaminated after Chernobyl accident, were adduced. Mean density of 137Cs contamination in two compared living areas were 111 and 200 kBq/m2 and mean external doses accumulated for 1986-2001 were 6.7 and 11.4 mGy correspondingly. Averaged thyroid doses receives by subjects of all age groups in the second area were approximately 1.5 times higher than in the first area; in the youngest group (0-1 year) the doses were 114.3 and 174.3 mGy. During 17 years cytogenetic investigation approximately from 30% to 60% of examined persons were observed the increased level of chromosome aberrations in lymphocytes of peripheral blood. Average frequency of unstable aberrations (acentrics, dicentrics and centric rings) constituted about 0.4 per 100 cells (0.22 per 100 cells in controls) during all period of observation. Level of marker aberrations (dicentrics and centric rings) was increased almost all times of study and varied within 0.04-0.19 per 100 cell (0.03 in control group). The parallel investigation of frequency of stable aberrations by FISH method showed up their level about 3 times exceeding observed dicentrics level. Comparably higher indexes of cytogenetic disturbances were revealed in group exposed in utero during period of accident.     

Genetic effects in the liquidators of consequences of Chernobyl Nuclear Power Plant accident

The purpose of the present research was the estimation of probable genetic consequences at the liquidators of the consequences of Chernobyl accident in 1986-1987. The research is made on two groups of the liquidators. The first group included the liquidators taking place on the account in the branch register and working now at the enterprises of a nuclear industry. The second group included 902 liquidators of consequences of Chernobyl accident in 1986 constantly living in the Ryazan area and which are taking place on permanent observation the account in regional hospital. For an estimation of probable genetic effects analyzed the data on frequency and outcomes pregnancy of the wives of the liquidators, on condition and on diseases of newborn, on switching intrauterine development defects (IDD). The analysis carried out depending on dozes of an irradiation: up to 5 cGy; 5-10 cGy and 10-25 cGy. Received materials testify, that at the liquidators, at a doze of an external irradiation 10-25 cGy, the determined effects--period long sterility, kept at a part them till 3 years come to light. The set of the received data, such as depending from the dose increase of frequency of spontaneous abortions and of inherent defects of development of newborn, the increase of frequency diseases of newborn and share newborn with low weight, allows to make a conclusion about an induction of genetic effects in sexual cells of the liquidators of consequences of Chernobyl accident at dozes of an external irradiation more than 10 cGy. Taking into account high biological efficiency of alpha-radiation (K = 20), and of beta-radiation (K = 2-4), the equivalent effective doze male gonads (testes) in 3-5 times is higher, than estimated only from external gamma-radiation.     

Thyroid cancer incidence among Chernobyl emergency workers: follow-up period 1986-2003

A vast amount of research articles devoted to the increase in childhood thyroid cancer incidence in the most contaminated by radionuclides territories of Belarus, Russia and Ukraine affected by the Chernobyl accident were published recent years. However, the amount of research studies of thyroid cancer incidence among the Chernobyl emergency workers (liquidators) is quite scanty. In the article results of the study of thyroid cancer incidence in the cohort of the Chernobyl liquidators (103427 persons) residing in 6 administrative regions of Russia (North-West, Volgo-Vyatsky, Central-Chernozemny, Povolzhsky, North-Caucasus and Urals) are described and discussed. For the period 1986-2003 eighty seven cases of thyroid cancer were detected in the cohort. Statistically significant excess of the incidence among liquidators over baseline incidence, SIR = 3.39 (95% CI: 2.73; 4.16), among men of Russia has been found. The highest thyroid cancer incidence (SIR = 6.49) was registered among liquidators who had been involved in mitigation works during April-July 1986. At the same time no statistically significant relationship between the incidence rate and external radiation dose, ERR = 1.68 (95% CI: -0.95; 6.46), was detected.     

The radiological situation before and after Chernobyl disaster

The nuclear reactor accident, which occurred on 26 April 1986 at Chernobyl, has been one of the greatest ecological disasters in human history. In our study we discussed the most recent data on the accident, and the natural and synthetic sources of radiation. According to the recent data, the air at Chernobyl had been contaminated with about 5300 PBq radionuclide activity (excluding rare gases), including 1760 PBq (131)I and 85 PBq (137)Cs. The highest radiation received by the liquidators (0.8-16 Gy), lower doses were received by the population which was evacuated or inhabited the contaminated areas (in which the level of (137)Cs activity deposited in the earth was 37 kBq/m(2)). In the European countries the highest mean radiation dose per year for the whole body in the first year after the accident was in Bulgaria (760 microSv), Austria (670 microSv) and Greece (590 microSv), while the lowest radiation dose was observed in Portugal (1.8 microSv) and Spain (4.2 microSv). In Poland the mean effective equivalent dose resulting from Chernobyl accident was 932 microSv and is close to the limited dose permitted in Poland, equalling 1 mSv/year. The highest radiation dose to thyroid was received by inhabitants of the states previously known as Bielskopodlaskie, Nowosadeckie and the north-east region of Poland. Lowest dose was received by inhabitants of the areas previously known as Slupski and Rzeszowski.     

Long-term follow-up cytogenetic survey and biological dosimetry in persons evacuated from 30-km Chernobyl NPP zone

The paper presents the results of the follow-up cytogenetic survey and biological dosimetry carried out in inhabitants of Pripiat' town and nearby villages, who were departured from the Chernobyl NPP 30-km exclusive zone during first days after the Chernobyl catastrophe. The unstable chromosome aberration level in inhabitants were significantly increased above control in terms up to 1 year after evacuation and declined gardually during next 14 years. In early period the cytogenetic damage frequency in evacuees showed no dependence on gender. The chromosome type aberration level appeared to be lower in young persons comparing with adults. The dicentrics plus centric rings yield had a positive correlation with duration of staying at Chernobyl zone. The average doses of protracted exposure were calculated from the dicentrics and centric rings yields; the dose estimations appeared to be 1.4 times higher in persons evacuated 3-11 days after the accident than that of in persons with shorter departure time. Uing the Bayesian analysis the probabilistic distribution of biological doses was constructed for the studied evacuees group. This distribution was characterized by a mean dose of 360 mGy, the modal doses of 200-450 mGy and 80% of probability density within the dose range 0-1000 mGy, that seems to be sufficient for considering the increased risk of late somatic radiation effects for this cohort.     

Cancer morbidity and mortality among the liquidators of the Chernobyl accident: estimation of radiation risks

The work focuses on the results of the analysis of the cancer incidence among the Chernobyl emergency workers residing in Russia during 1991-2001. The analysis is based on the data for the cohort of male emergency workers from 6 regions of Russia including 55718 persons with documented external radiation doses in the range of 0.001-0.3 Gy who worked within the 30-km zone in 1986-1987. The mean age at exposure for these persons was 34.8 years old and the mean external radiation dose 0.13 Gy. In this cohort 1370 cases of solid cancer were diagnosed. Three follow-up periods were considered: 1991-1995, 1996-2001 and 1991-2001. The second follow-up period was chosen to allow for a minimum latency period of 10 years. Risk assessments were performed for two control groups: the first control group ("external") represented incidence rates for corresponding ages in Russia in general and the second control group ("internal") consisted of emergency workers. The estimated standardized incidence ratio (SIR) is in good agreement with that of the control within 95% CI. The values of the excess relative risk per unit dose 1 Gy (ERR/Gy) for solid malignant neoplasms have been estimated to be 0.33 (95% CI: -0.39, 1.22) (internal control) for the follow-up period 1991-2001 and 0.19 (95% CI: -0.66, 1.27) for 1996-2001. The analysis of cancer morbidity was carried out for the cohort of 29003 emergency workers who took part in liquidation of the consequences of the Chernobyl accident from 26 April 1986 to 25 April 1987. It was shown that the excess relative risk of cancer deaths per unit dose 1 Sv (ERR/Sv) is equal to 1.52 (95% CI: 0.20, 2.85).     

A comparison of the number of chromatid aberrations with dose, estimated from the frequency of dicentrics, in the cytogenetic study of lymphocytes in subjects involved in the accident at the Chernobyl Nuclear Power Station

A study was made of the frequency of chromatid aberrations in lymphocyte culture of subjects affected by the Chernobyl accident as a function of dose estimated by the incidence of dicentrics. The average number of chromatid aberrations was nearly the same within the dose range from 0 to 5 Gy exhibiting a tendency towards growth with dose. A high individual variability of the chromatid aberration frequency was observed.     

Comparative results of thyroid ultrasound and laboratory studies in patients exposed to radiation

The paper presents the data of thyroid ultrasound and laboratory studies in 233 persons exposed to radiation: 63 X-ray physicians, 36 Chernobyl accident liquidators, 31 patients with lymphogranulomatosis, receiving radiotherapy, and 103 individuals (a control group) who were physicians of various specialties whose professional activity is unassociated with radiation factors. Thyroid changes were found in 67.7% of the examinees after gamma teletherapy and in 31% in the control group; among X-rat physicians and Chernobyl accident liquidators, the occurrence of thyroid changes was equal--44.4%. Direct radiation exposure of the thyroid in a dose of above 30 Gy led to the development of postradiation fibrosis (22.5%) and postradiation thyroiditis (32.3%) with thyroid dysfunction that is most commonly presented by hypothyroidism (22.45%). Autoimmune thyroiditis (11.1%) more predominantly with subclinical hypothyroidism, and diffuse thyroid hyperplasia (19.4%) resulted from mixed internal and external radiation. Thyroid changes revealed in X-ray physicians mainly appeared as nodular masses (22.2%) without functional impairments but to be followed up. It is recommended that the annual preventive examination protocol be supplemented by thyroid ultrasound studies in X-ray physicians.     

Restoration of pine plantations after effect of ionizing radiation in the region of the accident at the Chernobyl Atomic Energy Station

The main results of the 12-year radiation-genetic monitoring of radiobiological, cytogenetic, and genetic parameters in the Pinus sylvestris L. forest plantations from the zone of the accident at the Chernobyl nuclear power plant presented. Acute ionizing irradiation at doses > 1 Gy was shown to induce the formation of morphoses and depressed growth; at doses > 2 Gy, the reproductive ability of the trees declined. The radiobiological parameters showed a linear (or close to linear) dose-effect relationship. Acute irradiation at a dose of 0.5 Gy induced cytogenetic and genetic effects that were significantly higher than the corresponding control values. The relationship between the cytogenetic effects and the absorbed dose was exponential. The dependence of the mutation frequency at specific loci on the absorbed dose was described by a nonlinear curve. The results of cytogenetic analysis of sprouts obtained from seeds annually (1986-1998) collected in zones of slight, moderate, and strong damage of Pinus sylvestris L. are presented.     

Medical protection during radiation accidents: some results and lessons of the Chernobyl accident

Actions of medical radiation protection of liquidators of consequences of on Chernobyl atomic power station accident are analysed. It is shown, that during the early period of the accident medical protection of liquidators was provided by administration of radioprotectors, means of prophylaxis: of radioactive iodine incorporation and agent for preventing psychological and emotional stress. When carrying out decontamination and regenerative works, preparations which action is caused by increase of nonspecific resistance of an organism were applied. The lessons taken from the results of the Chernobyl accident, have allowed one to improve the system of medical protection and to introduce in practice new highly effective radioprotective agents.     

The distribution of individual radiation doses in liquidators of Chernobyl accident using cytogenetic analysis

The cytogenetic screening was carried out in 100 Chernobyl clean-up workers (liquidators) with registered doses during 1 year after exposure. The bayesian analysis has been applied for constructing the individual distribution of probability density for biological doses estimated from dicentric and centric ring yields in liquidators. The coincidence of the biological and registered dose has been found in 25% of cases; among the rest persons the documented doses exceeded the biological estimations in 25% of cases and the cytogenetic doses were higher than registered ones in 50% of cases. The total distribution of biological doses was constructed by pooling the individual data in 50 mGy dose intervals. The distribution obtained had the maximum at 300-350 mGy and contained 68% of probability density in the dose range 0-1000 mGy. The probabilistic approach in cohort biodosimetry showed the necessity of corrections in radiogenic risk assessment for Chernobyl liquidators. The advantages of bayesian technique for biodosimetrical treatment of cytogenetic data in conditions of small number of cells scored and low aberration yields induced by low dose irradiation were discussed.     

A cytogenetic follow-up study of the victims of a radiation accident in Goiania (Brazil)

A radiation accident involving a cesium-137 therapy source occurred in Goiania (Brazil) in September 1987, in which more than 50 individuals were exposed to moderate to high doses (0.2-7 Gy) of gamma-radiation. A cytogenetic technique (i.e., frequencies of dicentrics and rings in peripheral lymphocytes) was employed to estimate the absorbed radiation dose. The follow-up study extending over more than 1 year indicated a decline in the frequencies of dicentrics in the lymphocytes. Using chromosome-specific biotinylated library probes for chromosomes 1, 2, 8 and 19, we studied the frequencies of chromosomal translocations and deletions and the incidence of aneuploidy in the lymphocytes of exposed individuals. In some individuals there was a significant increase in the frequency of translocations and aneuploidy. In other experiments, in which the frequencies of HPRT mutations were determined in lymphocytes using the BrdU-labeling method, some individuals showed an increase (from about 2- to 50-fold) in mutant frequencies.