Chromosome aberrations and rogue cells in lymphocytes of Chernobyl clean-up workers

A cytogenetic analysis was performed on peripheral blood lymphocytes from 183 Chernobyl clean-up workers and 27 control individuals. Increased frequencies of chromosome aberrations were associated with exposure to radiation at Chernobyl, alcohol abuse and a history of recent influenza infection. However, only approximately 20% of Chernobyl clean-up workers had an increased frequency of dicentric and ring chromosomes. At the same time, an increased frequency of acentric fragments in lymphocytes of clean-up workers was characteristic. The use of multivitamins as dietary supplement significantly decreased the frequency of chromosome aberrations, especially of chromatid breaks. Rogue cells were found in lymphocytes of 28 clean-up workers and 3 control individuals. The appearance of rogue cells was associated with a recent history of acute respiratory disease (presumably caused by adenoviral infection) and, probably, alcohol abuse. Dicentric chromosomes in rogue cells were distributed according to a negative binomial distribution. Occurrence of rogue cells due to a perturbation of cell cycle control and abnormal apoptosis is suggested.     

The retrospective cytogenetic dosimetry using the results of conventional chromosomal analysis in Chernobyl clean-up workers

The paper presents the results of the cohortal biodosimetry carried out in 435 Chernobyl clean-up workers, who were surveyed with the conventional cytogenetic technique in terms from several days to 10 years after the end of their duties in the Chernobyl accident exclusive zone. An empirical model of the aberrant cell dynamics was utilized for the calculation of mean initial yields of dicentrics and centric rings in groups with different terms and duration of staying in the Chernobyl zone. Corresponding protracted irradiation doses estimated from aberration levels ranged from 79 to 670 mGy. The probabilistic distribution of the radiation doses was constructed by the applying the Bayesian analysis to initial individual chromosome exchange yields extrapolated to the exposure termination moment. This distribution was characterized by the mean dose about 460 mGy and maximum of probability density in the interval of 50-300 mGy. For the late somatic risk assessment in clean-up workers the probabilistic distribution of equivalentally-acute radiation doses was proposed; that had the mean value about 270 mGy, modal classes of 250-350 mGy and 99.8% of the probability density concentrated within the dose range from 0 to 1000 mGy.     

Doses of Ukrainian female clean-up workers with diagnosed breast cancer

The Chernobyl reactor accident in 1986 has caused significant exposure to ionizing radiation of the Ukrainian population, in particular clean-up workers and evacuees from the exclusion zones. A study aiming at the discovery of radiation markers of the breast cancer was conducted from 2008 to 2015 within a collaborative project by HZM, LMU, and NRCRM. In this study, post-Chernobyl breast cancer cases both in radiation-exposed female patients diagnosed at age less than 60 from 1992 to 2014 and in non-exposed controls matched for residency, tumor type, age at diagnosis, TNM classification as well as tumor grading were investigated for molecular changes with special emphasis to copy number alterations and miRNA profiles. Cancer registry and clinical archive data were used to identify 435 breast cancer patients among female clean-up workers and 14 among evacuees from highly contaminated territories as candidates for the study. Of these, 129 breast cancer patients fit study inclusion criteria and were traced for individual reconstruction of the target organ (breast) doses. The doses were estimated for 71 exposed cases (clean-up workers and evacuees from which biomaterial was available for molecular studies and who agreed to participate in a dosimetric interview) by the use of the well-established RADRUE method, which was adjusted specifically for the assessment of breast doses. The results of 58 female clean-up workers showed a large inter-individual variability of doses in a range of about five orders of magnitude: from 0.03 to 929 mGy, with median of 5.8 mGy. The study provides the first quantitative estimate of exposures received by female clean-up workers, which represent a limited but very important group of population affected by the Chernobyl accident. The doses of 13 women evacuated after the accident who did not take part in the clean-up activities (from 4 to 45 mGy with median of 19 mGy) are in line with the previous estimates for the evacuees from Pripyat and the 30-km zone.     

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.     

Chernobyl clean-up workers erythrocyte membrane lipid content at the remote period

Chernobyl Nuclear Power Plant accident clean-up workers were exposed to different radiation doses. Realization of remote effects depends on cellular membrane structure and function. We studied lipid composition of erythrocyte ghost and blood plasma in clean-up workers on the 12-th year after the accident. Groups of Chernobyl accident clean-up workers, non-irradiated patients with the same diseases and healthy controls were studied. Phospholipids were analyzed by two dimentional thin layer chromatography on silica gel. To analyse fatty acids and cholesterol gas chromatography was used. Total cholesterol and total phospholipids amounts in clean-up workers erythrocyte ghost were increased. The level of sphingomyelin and phosphatidylethanolamine raised. In some of the studied irradiated patients lysophosphatidylethanolamine appeared. The distribution of (diacyl)- and plasmalogen forms of phosphatidylcholine and phosphatidylethanolamine was not affected. The fatty acid composition changed slightly except 22:5 n-3, which level significantly increased and 22:5 n-6, which quantity lowered. The unsaturation index remains unchanged. No change in lipid composition of blood plasma was detected. All the changes in lipid composition of erythrocyte ghost of irradiated and unexposed patients were very similar. The obtained results confirm the suggestion about non-specific remote effects after exposure to low doses of ionizing irradiation.     

The distribution of chromosome damage, non-reciprocal translocations and clonal aberrations in lymphocytes from Chernobyl clean-up workers

In this paper we determined whether the frequencies of translocations and insertions are proportional to chromosome size in peripheral blood lymphocytes from Chernobyl nuclear accident clean-up workers and healthy unexposed control subjects. The frequency of aberrations among chromosomes 1, 2 and 4 in both groups was found to be significantly different from the distribution expected on the basis of chromosome size, although the difference was only marginally significant in controls. We also determined whether differences exist in aberration frequencies measured by two scoring systems: the classical method, where reciprocal exchanges are scored as one event, and PAINT, where each break junction is scored as a single event. The two scoring systems gave highly correlated results which yielded an interpretable arithmetic relationship between frequency measurements using the two systems. Approximately 34% of all translocations were observed to be non-reciprocal, and cells bearing clones of abnormal cells were observed in 6 of 198 subjects (3.0%). Our results demonstrate that clones of abnormal cells and the presence of non-reciprocal translocations contribute to the non-proportional distribution of radiation-induced and spontaneous cytogenetic damage.     

Impact of the Radiation Factor on Mean Survival Time for Chernobyl Clean-up Workers with Solid Cancer

Biology Bulletin - The aim of this study was to investigate the mean survival time for Chernobyl clean-up workers (liquidators) with diagnosed solid cancer. The cohort of liquidators contained...     

Vertical Distribution and Estimated Doses from Artificial Radionuclides in Soil Samples around the Chernobyl Nuclear Power Plant and the Semipalatinsk Nuclear Testing Site

For the current on-site evaluation of the environmental contamination and contributory external exposure after the accident at the Chernobyl Nuclear Power Plant (CNPP) and the nuclear tests at the Semipalatinsk Nuclear Testing Site (SNTS), the concentrations of artificial radionuclides in soil samples from each area were analyzed by gamma spectrometry. Four artificial radionuclides (²⁴¹Am, ¹³⁴Cs, ¹³⁷Cs, and ⁶⁰Co) were detected in surface soil around CNPP, whereas seven artificial radionuclides (²⁴¹Am, ⁵⁷Co, ¹³⁷Cs, ⁹⁵Zr, ⁹⁵Nb, ⁵⁸Co, and ⁶⁰Co) were detected in surface soil around SNTS. Effective doses around CNPP were over the public dose limit of 1 mSv/y (International Commission on Radiological Protection, 1991). These levels in a contaminated area 12 km from Unit 4 were high, whereas levels in a decontaminated area 12 km from Unit 4 and another contaminated area 15 km from Unit 4 were comparatively low. On the other hand, the effective doses around SNTS were below the public dose limit. These findings suggest that the environmental contamination and effective doses on the ground definitely decrease with decontamination such as removing surface soil, although the effective doses of the sampling points around CNPP in the present study were all over the public dose limit. Thus, the remediation of soil as a countermeasure could be an extremely effective method not only for areas around CNPP and SNTS but also for areas around the Fukushima Dai-ichi Nuclear Power Plant (FNPP), and external exposure levels will be certainly reduced. Long-term follow-up of environmental monitoring around CNPP, SNTS, and FNPP, as well as evaluation of the health effects in the population residing around these areas, could contribute to radiation safety and reduce unnecessary exposure to the public.     

Electron microscopy and ultracytochemistry of lymphocytes containing Gall bodies in the blood of patients with diabetes mellitus, Hodgkin disease and clean-up workers of the Chernobyl Atomic Electric Plant accident

Submicroscopic and ultracytochemical changes in lymphocytes containing Gall body complex in the cytoplasm, have been studied in the blood of patients with type 1 and 2 diabetes mellitus, Hodgkin disease, and clean-up workers of the Chernobyl accident. It has been shown that each pathological state was characterized by specific changes in the ultrastructure of Gall body complex, that pointed out its important role in the function of this type of lymphocytes and may be used as an additional cytological criterion in the estimation of T-immunity status.     

The problem of the transgeneration phenomenon of genome instability in sick children of different age groups after the accident at the Chernobyl Nuclear Power Plant

A complex genetic examination of children which belong to two cohorts and their parents were carried out. The first cohort included children and constantly living on territories contaminated with radionuclides (Novozybkov district, Bryansk region). They were subdivided in groups according to the ontogenetic age periods of development of their parents at the time of the Chernobyl accident. In the children born in 1986-1995 the level of aberrant genomes is significantly higher as compared to the control (p < 0.001). In children born in 1998-2002 the differences are insignificant (p > 0.05). The frequency of aberrant genomes had a tendency to decrease with the period of time between the birth date of a child and the moment of the accident. Analysis of the results of cytogenetic investigation for the same living on territories with different densities of radioactive contamination (zone I-- 627-688 kBq/m2, 137Cs and zone II-- 135-402 kBq/m2, 137Cs) revealed insignificant differences in the spectrum and average frequencies of chromosome aberrations. The second cohort included children born in 1987-1991 and 1993-2002 from irradiated fathers (Chernobyl clean-up workers) and unirradiated mothers living on territories without radionuclide contamination. These children also displayed increased frequencies of aberrant genomes as compared to the control (p < 0.001). The analysis of the dynamics years of birth of cytogenetic disturbances in the same cohorts of children showed the average frequencies of aberrant genomes remain higher than the control level. In most of the children of both cohorts the repair synthesis of genome DNA by gamma- and UV-radiation is reduced as compared to one in the children from the control group.     

The genotoxic risk of underground coal miners from Turkey

A cytogenetic monitoring study was carried out on a group of workers from a bituminous coal mine in Zonguldak province of Turkey, to investigate the genotoxic risk of occupational exposure to coal mine dust. Cytogenetic analysis, namely sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and micronucleus (MN) tests were performed on a strictly selected group of 39 workers and compared to 34 controls matched for gender, age, and habit. Smoking and age were considered as modulating factors. Both SCE and CA frequencies in coal miners appeared significantly higher than in controls. Similarly, there was a significant increase in the frequency of total micronuclei in exposed group as compared to control group. The effect of smoking on the level of SCE and MN was significant in the control group. A positive correlation between the age and the level of SCE was also found in controls. The frequencies of both SCE and CA were significantly enhanced with the years of exposure. The results of this study demonstrated that occupational exposure to coal mine dust leads to a significant induction of cytogenetic damage in peripheral lymphocytes of workers engaged in underground coal mining.     

Influence of delta-aminolevulinic acid dehydratase (ALAD) polymorphism on the frequency of sister chromatid exchange (SCE) and the number of high-frequency cells (HFCs) in lymphocytes from lead-exposed workers

In this study, the cytogenetic response to lead exposure in storage battery manufacturing workers carrying different alleles of delta-aminolevulinic acid dehydratase (ALAD 1 and ALAD 2) was evaluated. The cytogenetic response was measured by analysis of the frequency of sister chromatid exchange (SCE) and the number of high-frequency cells (HFCs) in peripheral blood lymphocytes from workers occupationally exposed to lead. A total of 71 voluntary male workers were enrolled in the study. According to our genotype analysis, 50 workers had the ALAD 1-1 genotype and 21 workers had the ALAD 1-2 genotype. In spite of the statistically insignificant difference in mean values of SCE per cell between ALAD 1-1 and ALAD 1-2 workers, the percentage of HFC (HFC (%)) was statistically (chi2-test, P<0.05) higher in ALAD 1-1 workers. The control group was selected among voluntary male office workers (n = 20) and genotyping was also performed for this group in order to rule out the possibility that ALAD 1-1 subjects had a higher HFC (%) than ALAD 1-2 carriers, independent of the exposure to lead. Accordingly, 11 control workers had the ALAD 1-1 genotoype and 9 workers had ALAD 1-2. The differences in mean values of SCE per cell and HFC (%) were not statistically significant when the two genotypes in the control group were compared. On the basis of this result we suggest that ALAD 1-1 subjects might be more susceptible to cytogenetic effects of lead exposure than ALAD 1-2 subjects. There were no ALAD 2-2 subjects in the exposed and control groups.     

The genotoxic risk of underground coal miners from Turkey

A cytogenetic monitoring study was carried out on a group of workers from a bituminous coal mine in Zonguldak province of Turkey, to investigate the genotoxic risk of occupational exposure to coal mine dust. Cytogenetic analysis, namely sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and micronucleus (MN) tests were performed on a strictly selected group of 39 workers and compared to 34 controls matched for gender, age, and habit. Smoking and age were considered as modulating factors. Both SCE and CA frequencies in coal miners appeared significantly higher than in controls. Similarly, there was a significant increase in the frequency of total micronuclei in exposed group as compared to control group. The effect of smoking on the level of SCE and MN was significant in the control group. A positive correlation between the age and the level of SCE was also found in controls. The frequencies of both SCE and CA were significantly enhanced with the years of exposure. The results of this study demonstrated that occupational exposure to coal mine dust leads to a significant induction of cytogenetic damage in peripheral lymphocytes of workers engaged in underground coal mining.     

Cytogenetic damage in workers from a coal-fired power plant

The aim of this study was to investigate the genotoxic risk to workers occupationally exposed to coal combustion products in Afsin-Elbistan A power plant, located in south-eastern Turkey. We analysed chromosomal aberrations (CAs), polyploidy, sister-chromatid exchanges (SCEs), and micronuclei (MN) in 48 male workers without a history of smoking, tobacco chewing, or alcohol consumption. The results were compared with a control group of 30 healthy male individuals without exposure to any known genotoxic agents. The mean frequencies of CA, polyploidy, SCEs (P<0.01), and MN (P<0.05) were significantly higher in workers than in the control group, by the Mann-Whitney U-test. Spearman's rho correlation analysis revealed a significant increase in the frequency of CA and MN with increasing years of exposure (P<0.05). However, there was no significant effect of age on the cytogenetic markers analysed in both groups (P>0.05). The data obtained from this study clearly showed chromosomal hazard in the peripheral lymphocytes of workers exposed to coal combustion products in Afsin-Elbistan A power plant for several years. This cytogenetic damage might be attributed to the cumulative effects of several substances due to chemical complexity of the coal ash and gaseous emissions rather than a specific substance.     

Chromosomal aberrations and sister-chromatid exchanges in Lithuanian populations: effects of occupational and environmental exposures

Cytogenetic analysis of chromosomal aberrations (CA) in 175,229 cells from 1113 individuals, both unexposed and occupationally or environmentally exposed to heavy metals (mercury and lead), organic (styrene, formaldehyde, phenol and benzo(a)pyrene) and inorganic (sulfur and nitrogen oxides, hydrogen and ammonium fluorides) volatile substances and/or ionizing radiation was performed. In addition, 11,250 cells from 225 individuals were scored for the frequency of sister-chromatid exchanges (SCE). Increased frequencies of CA were found in all occupationally exposed groups. A principal difference between the exposure to heavy metals and organic substances was found: increase in the CA frequency was dependent on duration of exposure to mercury but not dependent on duration of exposure to styrene, formaldehyde and phenol. A higher CA incidence was found in lymphocytes of children living in the vicinity of a plant manufacturing phosphate fertilizers. This indicates that children are a sensitive study group for the assessment of environmental exposure. However, the results of SCE analysis in these children were inconclusive. Exposure to ionizing radiation was found to cause chromosome breaks and chromatid exchanges in Chernobyl clean-up workers and chromatid breaks, chromatid exchanges, dicentric chromosomes and chromosome translocations in workers from the Ignalina Nuclear Power Plant. The increased frequency of chromatid exchanges in individuals exposed to ionizing radiation was quite unexpected. This may be attributed to the action of some unrecognized life-style or occupational factors, or to be a result of radiation-induced genomic instability. Also an increased SCE frequency was found in lymphocytes of Chernobyl clean-up workers.     

Cytogenetic analysis of peripheral blood lymphocytes in workers exposed to benzene

In the present study, the method of cytogenetic analysis of peripheral blood lymphocytes was used to investigate 66 workers exposed to benzene, and 20 individuals selected from general population from the same locality, not exposed to particular mutagenic or carcinogenic agents (control group). Altogether, 8,600 metaphases were analysed. Frequencies of aberrant cells, including chromatide and chromosomal breaks, and chromatide and chromosomal exchanges, were scored in both groups. A very slight increase in aberrant cell frequencies (2.152% aberrant cells) was observed in the professional exposure group as compared to the control group (1.6% aberrant cells). Increased frequencies of aberrant cells were found in smokers of both the benzene-exposed and the control group. The differences were however not significant. In addition to cytogenetic examination, the workers underwent a general examination of their health condition (preventive examination). Benzene exposure seemed to have no injurious effect on the state of health of exposed workers. Biochemical and haematological tests gave normal values.     

Cytogenetic monitoring of industrial populations potentially exposed to genotoxic chemicals and of control populations

Currently the most applied technique for monitoring biological effects of exposure to genotoxic chemicals in industrial workers is the measurement of chromosome aberrations in peripheral blood lymphocytes. In the Shell petrochemical complex in The Netherlands cytogenetic monitoring studies have been carried out from 1976 till 1981 inclusive, in workers potentially exposed to a variety of genotoxic chemicals, i.e. vinyl chloride, ethylene oxide, benzene, epichlorohydrin, epoxy resins. Average exposure levels to these chemicals were well below the occupational exposure limits. Results of these studies indicate that no biologically significant increase in the frequencies of chromosome aberrations in the exposed populations occurred compared with control populations. Our experience with this methodology has shown that the results of chromosome analyses are difficult to interpret, due to the variable and high background levels of chromosome aberrations in control populations and in individuals. It is concluded that the method is not sufficiently sensitive for routine monitoring of cytogenetic effects in workers exposed to the low levels of genotoxic compounds.     

Genotoxicity of pesticides: a review of human biomonitoring studies

Pesticides constitute a heterogeneous category of chemicals specifically designed for the control of pests, weeds or plant diseases. Pesticides have been considered potential chemical mutagens: experimental data revealed that various agrochemical ingredients possess mutagenic properties inducing mutations, chromosomal alterations or DNA damage. Biological monitoring provides a useful tool to estimate the genetic risk deriving from an integrated exposure to a complex mixture of chemicals. Studies available in scientific literature have essentially focused on cytogenetic end-points to evaluate the potential genotoxicity of pesticides in occupationally exposed populations, including pesticide manufacturing workers, pesticide applicators, floriculturists and farm workers. A positive association between occupational exposure to complex pesticide mixtures and the presence of chromosomal aberrations (CA), sister-chromatid exchanges (SCE) and micronuclei (MN) has been detected in the majority of the studies, although a number of these failed to detect cytogenetic damage. Conflicting results from cytogenetic studies reflect the heterogeneity of the groups studied with regard to chemicals used and exposure conditions. Genetic damage associated with pesticides occurs in human populations subject to high exposure levels due to intensive use, misuse or failure of control measures. The majority of studies on cytogenetic biomarkers in pesticide-exposed workers have indicated some dose-dependent effects, with increasing duration or intensity of exposure.Chromosomal damage induced by pesticides appears to have been transient in acute or discontinuous exposure, but cumulative in continuous exposure to complex agrochemical mixtures.Data available at present on the effect of genetic polymorphism on susceptibility to pesticides does not allow any conclusion.     

Cytogenetic analysis of peripheral blood lymphocytes in workers exposed to vinyl chloride

In the present study, the method of cytogenetic analysis of peripheral blood lymphocytes was used to examine 43 workers exposed to vinyl chloride monomer (average exposure 11.2 years) and 22 subjects selected from the same locality (control group). A total number of 8650 metaphases were analysed. All cytogenetic parameters examined were increased in the exposed group as compared to the control group and 3 parameters, chromatid breaks, percentage of aberrant cells and breaks per cell, were significantly increased (P less than 0.001).