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.     

Chromosome aberrations in lymphocytes and clastogenic factors in plasma detected in Belarus children 10 years after Chernobyl accident

In 1996, 10 years after Chernobyl accident, a cytogenetic analysis was carried out to assess whether chromosome aberrant cells (CA) were still detectable in the lymphocytes and clastogenic factors (CFs) were present in the plasma of children coming from Gomel (Belarus), one of the most heavily contaminated regions. Furthermore, the possible contribution of plasmatic CFs to the amount of CA was investigated. The presence of CA was examined in the lymphocytes from 29 thyroid tumour-affected children and 41 healthy children (local controls). Thirty healthy children living in Pisa (Italy) were enrolled in the study as additional controls from an uncontaminated area. No significant difference was observed between the two control groups, whereas a significantly increased frequency of CA was found in the tumour-affected children, as compared with Gomel and Pisa controls (χ²-test, p<0.001). However, when soil contamination level was taken into account, the chromosome type CA frequency observed in tumour-affected children coming from the more contaminated areas (>4 Ci/km²) resulted significantly higher than that in other children, either affected or not (p=0.003). The presence of CFs was analyzed on the plasma ultrafiltrate from 41 children. 7/10 (70%) plasma samples from tumour-affected children and 17/23 (74%) Gomel controls resulted to possess clastogenic activity irrespective of soil contamination levels. No activity was detected in the plasma of eight Pisa controls (0%). The difference between both Gomel groups and Pisa controls was highly significant (p=0.002). A borderline, but not statistically significant correlation (p=0.08) was observed between basal CA frequency and CF potency, which became significant (p=0.03) when only chromosome type of aberrations was considered. We conclude that, although the presence of CFs in the plasma of these children might be partly responsible of the cytogenetic effects observed, the main source of damage has considered to be do to the previous and/or continuous exposure to environmental radiocontaminants. Tumour-affected children may represent a subset of the population either more sensitive to clastogenic damage or exposed to higher levels of contaminants.     

Clinical and experimental parallels between immunological observations of irradiated animals and patients injured during Chernobyl accident

Immunological parameters in different periods of acute radiation syndrome (ARS) of experimental animals and Chernobyl reactor accident-injured patients have been studied. 148 patients and experimental animals (123 dogs and 198 monkeys) were observed after radiation exposure of different levels (from a sub-lethal dose to the minimal absolute lethal dose). We have found the increase in the C-reactive protein, fluctuation of normal antibody titers and the complement in blood serum, as well as the growing number of skin microbes after exposures to lethal doses. Experimental results match clinical data in terms of ARS progress phases but differ from the latter in terms of the time of clinical manifestations. The highest rate of clinical manifestations is observed on the 7-14 days for experimental animals (rats, dogs and monkeys) and on the 20-30 days for patients after radiation exposure. Regenerative processes in animals run faster than those in humans.     

Chromosome aberrations in lymphocytes and clastogenic factors in plasma detected in Belarus children 10 years after Chernobyl accident

In 1996, 10 years after Chernobyl accident, a cytogenetic analysis was carried out to assess whether chromosome aberrant cells (CA) were still detectable in the lymphocytes and clastogenic factors (CFs) were present in the plasma of children coming from Gomel (Belarus), one of the most heavily contaminated regions. Furthermore, the possible contribution of plasmatic CFs to the amount of CA was investigated. The presence of CA was examined in the lymphocytes from 29 thyroid tumour-affected children and 41 healthy children (local controls). Thirty healthy children living in Pisa (Italy) were enrolled in the study as additional controls from an uncontaminated area. No significant difference was observed between the two control groups, whereas a significantly increased frequency of CA was found in the tumour-affected children, as compared with Gomel and Pisa controls (chi 2-test, p < 0.001). However, when soil contamination level was taken into account, the chromosome type CA frequency observed in tumour-affected children coming from the more contaminated areas (> 4 Ci/km2) resulted significantly higher than that in other children, either affected or not (p = 0.003). The presence of CFs was analyzed on the plasma ultrafiltrate from 41 children. 7/10 (70%) plasma samples from tumour-affected children and 17/23 (74%) Gomel controls resulted to possess clastogenic activity irrespective of soil contamination levels. No activity was detected in the plasma of eight Pisa controls (0%). The difference between both Gomel groups and Pisa controls was highly significant (p = 0.002). A borderline, but not statistically significant correlation (p = 0.08) was observed between basal CA frequency and CF potency, which became significant (p = 0.03) when only chromosome type of aberrations was considered. We conclude that, although the presence of CFs in the plasma of these children might be partly responsible of the cytogenetic effects observed, the main source of damage has considered to be do to the previous and/or continuous exposure to environmental radiocontaminants. Tumour-affected children may represent a subset of the population either more sensitive to clastogenic damage or exposed to higher levels of contaminants.     

Chromosome aberration frequency in children with chronic thyroiditis born before and after the accident at the Chernobyl nuclear reactor

Children with chronic thyroiditis born before and after Chernobyl accident have been investigated cytogenetically using G-banding staining. It was shown that the chromosome instability and sensitivity to cesium radioisotopes increased and the pathological process in a thyroid gland implemented in persons exposed to 131I in their childhood and living in iodine-deficient territories.     

Mini-and microsatellite mutations in children from Chernobyl accident cleanup workers

Knowledge about possible genotoxic effects of low-dose radiation on the human germline is limited and relies primarily on extrapolations from high-dose exposures. To test whether ionizing radiation can cause paternal genetic mutations that are transmitted to offspring, we enrolled families of 88 Chernobyl cleanup workers exposed to ionizing radiation. We analyzed DNA isolated from lymphocytes for mutations via DNA blotting with the multi-locus minisatellite probes 33.6 and 33.15 and via PCR in a panel of six tetranucleotide repeats. Children conceived before and children conceived after their father's exposure showed no statistically significant differences in mutation frequencies. We saw an increase in germline microsatellite mutations after radiation exposure that was not statistically significant. We found no dependence of mutation rate on increasing exposure. A novel finding was that the tetranucleotide marker D7S1482 demonstrated germline hypermutability. In conclusion, our results do not support an increased level of germline minisatellite mutations but suggest a modest increase in germline mutations in tetranucleotide repeats. Small sample size, however, limited statistical power.     

Postnatal effects in children irradiated during the intra-uterine development, as a result of failure at the Chernobyl NPP

Somatic and genetic effects at children who have undergone the influence of ionizing radiation during in utero development and at the subsequent stages ontogenesis are investigated, in view of dozes of the general irradiation and equivalent dozes of an irradiation of red bone brain. 1144 children were examined: 1st group consisted of children who have been born from women pregnant at the moment of failure, evacuated from Pripyat; 2nd group included children who have been born from women pregnant at the moment of failure, stayed to live in a zone of the strict radiation control; 3rd group was the control group--children who have been born in 1986, living in safe region of the Ukraine according to radiation conditions. The presence of direct correlation link between quantity of small anomalies of the development and the total radiation dose of the fetus (R = 0.61, p < 0.002) and inverse link with fetus age at the moment of radiation factor effect (R = -0.53, p < 0.003) has been established. Significant correlation links between the total radiation dose and the level of children health (R = 0.45, p < 0.03); the equivalent radiation dose of the red bone marrow and the frequency of damages in the chromosomal apparatus of the somatic cells (1st group--R = 0.51, p < 0.02; 2nd group--R = 0.62, p < 0.002) have been revealed.     

Effect of natural b-carotene supplementation in children exposed to radiation from the Chernobyl accident

Attempts were made to evaluate 709 children (324 boys and 385 girls) who had been exposed long-term to different doses of radiation during and after the Chernobyl accident and had moved to Israel between 1990 and 1994. Upon arrival, all of them underwent a check-up for most common clinical disorders and were then divided into three groups according to their residences (distance from the reactor) and the level of irradiation exposure: no radiation, <5 Ci/m², and >5 Ci/m², respectively. Blood serum analyses for total carotenoids, retinol, α-tocopherol and oxidized conjugated dienes in 262 of the children showed increased HPLC levels of conjugated dienes, indicating increased levels of oxidation of in vivo blood lipids in children from the contaminated areas. The levels were higher in girls than in boys. Some 57 boys and 42 girls were given a basal diet with a diurnal supplementation of 40 mg natural 9-cis and all-trans equal isomer mixture β-carotene in a capsulated powder form of the alga Dunaliella bardawil, for a period of 3 months. Blood serum analyses were regularly conducted before supplementation to determine the baseline effect of radiation exposure to the children, after 1 and 3 months of natural β-carotene supplementation. After supplementation, the levels of the oxidized conjugated dienes decreased in the children's sera without any significant changes in the level of total carotenoids, retinol or α-tocopherol. Other common blood biochemicals were within the normal range for all tests and no statistical differences before or after supplementation of β-carotene were noted. High pressure liquid chromatography (HPLC) analyses for carotenoids in the blood detected mainly oxycarotenoids, and to a lesser extent, all-trans β-carotene, α-carotene, but not 9-cis β-carotene. The results suggest that irradiation increases the susceptibility of lipids to oxidation in the Chernobyl children and that natural β-carotene may act as an in vivo lipophilic antioxidant or radioprotector. Received: 20 March 1998 / Accepted in revised form: 1 August 1998     

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.     

Perinatal mortality in Germany following the Chernobyl accident

Perinatal mortality in Germany was investigated with respect to a possible relationship to the nuclear accident in Chernobyl on April 26, 1986. Using annual data of perinatal mortality, a trend analysis based on an appropriately chosen statistical model was performed which showed a significant increase in 1987. In addition, we calculated the cesium concentration in women's bodies using data of the cesium concentration in milk. We found two peaks of cesium concentration that were associated with the observed two peaks of monthly perinatal mortality data with a delay of 7 months. Received: 14 October 1994 / Accepted in revised form: 14 October 1996     

Infant leukemia in Belarus after the Chernobyl accident

Petridou et al. [1] have reported an increase in infant leukemia in Greek children born between 1/7/86 and 31/12/87 and have linked this increase to in utero radiation exposure due to the Chernobyl accident. Subsequently, Michaelis et al. [2] have reported a similar trend for Germany but found that it was not correlated to the levels of contamination. For Belarus, which was much more severely affected, a similar but much weaker trend is found. Received: 2 January 1998 / Accepted in revised form: 23 January 1998     

Genetic effects of bystander factors from the blood sera of people irradiated as the result of the Chernobyl accident

The purpose of this work was the analysis of the effects of bystander factors from blood sera of people affected by the Chernobyl accident on human keratinocyte cell culture (HPV-G cells). A new method was developed for evaluation of the bystander factor presence in vivo in blood of the people irradiated by the Chernobyl accident. Affected population groups included liquidators of the Chernobyl accident and people living and working in areas of the Gomel region contaminated by radionuclides. The analysis has shown that bystander factors persist in Chernobyl liquidator blood samples for more than 20 years since irradiation. The data suggest that blood sera contain bystander factors, which are able to induce micronuclei and decrease the metabolic activity of HPV-G cells.     

Cytogenetic and carcinogenic effects in liquidators of Chernobyl accident

A tendency of the increasing frequency of malignant neoplasms in liquidators at low radiation doses was found. The dose-effect dependence of the frequency of radiation markers (dicentric chromosomes) in lymphocytes of peripheral blood was revealed only in a group of liquidators of the ChNPP accident with malignant neoplasms in remote terms.     

Delayed effect of prenatal irradiation on the critical organs functional state in children after Chernobyl accident

Some indexes of a metabolism in 186 children exposed in utero through the Chernobyl accident were investigated ten years after the irradiation. All the children (basic and control groups) live in the territory with contamination less than 15 Ci/km2. It was shown, that the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and the level of bilirubin (conjugated and unconjugated) differed from the corresponding indexes in the control group (p < 0.05). These change depended on sex. The correlation between the levels of the total bilirubin, activity of the ACT, ALT in serum and absorbed doze to the thyroid of fetus was found (correlation coefficient > -0.8, p < 0.05). The linear regression equations for these three indexes are straight line: the total bilirubin, ACT and ALT decreased with the increase of the absorbed dose to the thyroid of fetus (p < 0.05). The relationship between the all indexes in serum and effective doze and levels of cesium accumulation was not detected.     

Chernobyl, the pathology of a nuclear accident

The accident at the Chernobyl nuclear power plant took place more than 20 years ago, on April 26th 1986, but its effects are still being felt, and its consequences influence the debate on nuclear power generation. The consequences for those working to contain the accident resembled those after the atomic bomb, 28 died from acute radiation sickness, and a further approximately 20 have died from the consequences of whole body radiation. The consequences for the millions exposed to high levels of fallout were quite different from those after the atomic bomb, and the talk will consider particularly the dramatic rise in thyroid carcinoma; currently estimated as about 4 000 cases. Fortunately only a small proportion has died from the disease. Initial studies concentrated on validating the diagnoses, later studies have shown a link between the molecular and morphologic pathology, the latent period and the aggressiveness of the tumours. These points will be reviewed, together with the link between radiation and thyroid carcinogenesis, and the possible future effects. The thyroid cancers are of particular significance because they represent the largest number of human tumours of one type due to one cause on one date that has ever occurred.     

Chromosome instability in Candida albicans

Candida albicans maintains genetic diversity by random chromosome alterations, and this diversity allows utilization of various nutrients. Although the alterations seem to occur spontaneously, their frequencies clearly depend on environmental factors. In addition, this microorganism survives in adverse environments, which cause lethality or inhibit growth, by altering specific chromosomes. A reversible loss or gain of one homolog of a specific chromosome in this diploid organism was found to be a prevalent means of adaptation. We found that loss of an entire chromosome is required because it carries multiple functionally redundant negative regulatory genes. The unusual mode of gene regulation in Candida albicans implies that genes in this organism are distributed nonrandomly over chromosomes.     

Molecular and cellular consequences of the Chernobyl accident

In this paper the results of the Chernobyl accident investigation 5-10 and 24 years after are summarized. The genomic instability, adaptive response formation, genome damage and oxidative status have been investigated. The studies were performed on cells in culture, mice, children and adults living in contaminated areas and liquidators. On cells in culture after exposition in the accident zone and culturing thereafter in laboratory conditions the cell proliferative activity decrease; the late cell death, the frequency of cells with micronuclei and giant cells increasing have been observed. In the progeny of exposed cells the enhancement of radiosensitivity has been noticed. So we can suppose that in cultured cells exposition in the zone of the accident the genomic instability is induced which results in many disturbances. At the organism level in mice exposed in the Chernobyl zone the radiosensitivity increase and the decrease of endotheliocytes density in brain tissue has been observed. On the stimulated by PHA blood lymphocytes of children the increase of the frequency of cells with micronuclei more than 2 time have been noticed. In all groups investigated, the decrease of individuals with significant adaptive response was observed. In children and adults inhabitants the increase of radiosensitivity after low dose of irradiation has been noticed. 24-year after the accident it was discovered that in liquidators lymphocytes the frequency of cells with micronuclei, with chromosome type aberrations, with DNA double strand breaks have been increased; the reactive oxygen species (ROS) were decreased in comparison with the control population. We can suppose that genomic instability induced in residents of contaminated regions and liquidators long after the accident results in the genetic apparatus damage, radiosensitivity enhancement, hypoxia that represent risk factors and increase the probability of tumour and non-tumour diseases. The development of these pathological processes may happen in much more remote periods.     

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.     

Very high mutation rate in offspring of Chernobyl accident liquidators

Exposure to ionizing radiation has long been suspected to increase mutation load in humans. Nevertheless, such events as atomic bombing seem not to have yielded significant genetic defects. The Chernobyl accident created a different, long-term exposure to radiation. Clean-up teams (or 'liquidators') of the Chernobyl reactor are among those who received the highest doses, presumably in some combination of acute and chronic forms. In this study, children born to liquidator families (currently either in the Ukraine or Israel) conceived after (CA) parental exposure to radiation were screened for the appearance of new fragments using multi-site DNA fingerprinting. Their sibs conceived before (CB) exposure served as critical internal controls, in addition to external controls (non-exposed families). An unexpectedly high (sevenfold) increase in the number of new bands in CA individuals compared with the level seen in controls was recorded. A strong tendency for the number of new bands to decrease with elapsed time between exposure and offspring conception was established for the Ukrainian families. These results indicate that low doses of radiation can induce multiple changes in human germline DNA.     

Complex cytogenetic characteristic of people suffered from Chernobyl accident

A cytogenetic study was performed on Chernobyl cleanup workers, on their children, on persons evacuated from contaminated aeria (adult and children), on so named "veterans of particular risk" irradiated due to the accidents on the nuclear plant, testing of nuclear weapons etc. and on control donors. The yield of stable (FISH analysis) and of unstable chromosome aberrations, micronuclei in both lymphocytes and erythrocytes, HPRT mutations was found to be increased in exposed groups as compared to control ones. In children of liquidators and in evacuated children we observed genomic instability and increased in vitro chromosomal radiosensitivity. Acceleration of age accumulation of translocations characterized the exposed population in comparison with control group. People with the highest level of routine chromosome aberrations had cardiovascular and digestive diseases more often likely than those with the lowest level. In frame of International Project ECP-6--"Biological dosimetry" the dose-responses for dicentrics and translocations were constructed in dose range 0-100 cGy of gamma-irradiation on the base of data of 8 laboratories. On cancer patients undergone whole-body gamma-irradiation (every day at the dose 11.5 cGy to a total of dose 57.5 cGy) we constructed the dose-responses for the dicentrics and translocations and compared them with the dose-responses for these aberrations after the in vitro irradiation of lymphocytes of the same patients. For the dicentrics the effectiveness of the in vivo irradiation was less than of the in vitro one. No differences were found for translocations.