Specific changes in auditory cognitive evoked potentials in those who participated in the liquidation of the chernobyl accident: I. Analysis of the early N1 component

The amplitude and temporal parameters of the N1 component of the auditory cognitive evoked potential (EP) were analyzed in ten people who participated in the elimination of the consequences of the Chernobyl accident (the liquidators) and ten healthy subjects aged 47 ± 6.0 and 50.5 ± 4.0 years, respectively. In the liquidators of the Chernobyl accident, the amplitudes of the N1 component of the auditory EP were decreased in all cortical areas. This decrease was the greatest in the central and frontal areas. The changes in response to stimuli of different significances in the liquidators were inverted as compared to the healthy subjects of the same age. The differences between the control group and the liquidators were the most pronounced in the temporal characteristics of the N1 component. The latent periods (LPs) for all stimuli presented under all experimental conditions were significantly shorter in the group of liquidators, and this effect was even stronger for the significant stimulus in the case of stimulus counting. In the liquidators, the maximum changes in the LPs of the N1 component were observed in the frontal area of the left hemisphere, and they were associated with an inversion of the LP asymmetry. Changes in this parameter were smaller in the central areas and were similar in the parietal areas in both groups studied. Changes in the amplitude and temporal characteristics of the N1 component of the auditory cognitive EP observed in the liquidators of the Chernobyl accident indicate the impairments of their involuntary attention and its capacity due to weakening of inhibition processes as compared to healthy subjects. This effect is similar to that found in elderly subjects. Our data support the hypothesis on the accelerated aging of the brain in the liquidators of the Chernobyl accident due to the effect of low doses of irradiation. The data also suggest that irradiation results in pathological aging.     

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.     

Delayed medical consequences of the Chernobyl accident in Armenia. Assessment of life quality and accelerated biological aging of accident liquidators

In this paper, some final results of 25-year investigations carried out in Scientific Centre for Radiation Medicine and Burns MH RA (SCRMB) on the Armenian cohort of the Chernobyl accident consequences liquidators are shown. These results show that health conditions of the liquidators became worse during the whole observation period. A considerable development of both pathological states atypical of radiation damages and diseases, which may be considered as radiation-induced ones, was determined. Rise of the sickness rate of almost all organism systems, first of all, nervous, cardiovascular, respiratory and digestive ones, was observed. In 70% of liquidators the main disease was primarily detected after working on CNPP. In the intervening years, the average number of diagnoses per 1 liquidator increased from 1.5 in 1987 to 7-8 in the recent time. In addition to the detected diseases, particular functional shifts in neuropsychological and vegetative status of the liquidators were observed. The overwhelming majority of them have increased tonicity of the sympathetic vegetative nervous system, asthenic and depressive syndromes occurring in the form of weakness, somnolence, mood instability, mental capacity decrease, and memory defects. In the paper, the results of investigations aimed at clarification of changes in biological aging processes of the liquidators and assessment of their "life quality" features in terms of physical, psychical and social welfare are considered. Biological aged-related passportization in a definite part of liquidators elucidated an accelerated aging rate. The studies were performed with the help of SF-36 inquirer and indicated that health status aggravation of the liquidators also affected their life satisfaction. The "life quality" indices of the liquidators significantly concede the overall average standards by both physical health and psychical and social welfare scales.     

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.     

FISH analysis in verification of recorded doses in liquidators of Chernobyl accident

With the help of the FISH technique the Official Dose Records (ODR) in 40 liquidators from the National (18 persons) and Military (22 persons) Registers were verified. In the civil liquidators the cases with the overestimated individual ODR were predominated while in the liquidators from the Military Register the cases with underestimation of the ODR in comparison with biological irradiation doses were prevailed. The both groups were considered as true "high-dose" ones with radiation exposure that exceed permissible levels for an accident.     

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 significance of cytogenetic investigation for the estimation of Chernobyl accident consequences

The results of the cytogenetic investigation of people, which were exposed to radiation in the result of the Chernobyl NPP accident, were presented. Also the possibilities of the application of cytogenetic findings for dose estimations and for the prediction of the radiation influence consequences were examined. During the period of time since 1986 till 2004 the cytogenetic investigations of 1724 liquidators participating in the liquidation works after the Chernobyl accident were carried out. The radiation dose estimated by the frequency of dicentrics in 1986 was about 0.16 Gy. The doses for liquidators were determined by the frequency of translocations (FISH method) during the period from 1992 till 1995. For liquidators who worked in Chernobyl only in 1986 the average dose of radiation was about 0.19 Gy and for liquidators who worked repeatedly during the period from 1986 till 1995 - 0.39 Gy. There was shown that during the whole period of investigation (1986-2004) the frequency of dicentrics in peripheral blood lymphocytes was significantly higher than the control level. The cytogenetic investigation of Bryansk region inhabitants which was carried out in 1992-1994 discovered heightened value in 5 times than the control one. Findings are of great importance for the prediction of ill effects of radiation and for the development of sensitive criterions for early exposure disturbances in state of health.     

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.     

The connection between molecular-cellular parameters and immune status of liquidators after Chernobyl accident

The genome damage (the frequencies of cells with micronuclei (MN), chromosome aberrations, the level of DNA double-strand breaks (DSB DNA), the concentration of reactive oxygen species (ROS) and 28 immunological parameters have been studied on the blood lymphocytes of Chernobyl accident liquidators. The purpose of this article was the investigation of cytogenetic, molecular changes of blood lymphocytes of irradiated individuals 24 years after accident, examination it there are correlation between genome damage and immunological parameters. It was shown that in lymphocytes of liquidators the frequencies of cells with MN and with all type of chromosome aberrations didn't differ from the lymphocytes of nonirradiated individuals, but the frequency of chromosome aberration type was increased, the level of DSB DNA was increased too. The concentration of ROS is decreased. The percent of cytotoxic CD8(+)-T-lymphocytes, natural killer cells (CD16(+)-lymphocytes), CD3+ CD16+ CD56+ (NK-T-cells), that posses antivirus and antitumor activity--HLA-DR+, regulatory T-lymphocytes (CD4+ CD25+high) in liquidators significantly increases. The level of serum immunoglobulin (Ig A) significantly increases too. The index of immune regulation, meaning of phagocyte neutrophil (FAN) and macrophage activity decreases. In liquidators there are significant correlation between the frequencies of cells with MN and the content of regulatory T-lymphocytes (p < 0.05), between the concentrations of ROS and activated T-lymphocytes. More connection is on the tendency level (p < 0.10): the frequency of chromosome aberrations, the DSB DNA level with natural killer cells and regulatory T-lymphocytes; the frequency of cells with MN and DSB DNA and FAM. We can suppose that genomic instability induced by the liquidators of Chernobyl accident consequences 24 years ago manifests now as increased genome damage and oxidative status decrease that can result in imbalance of cells and humoral immune status, disturbancies of health.     

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)).     

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.     

The number of nucleoli in peripheral blood lymphocytes of the Chernobyl accident liquidators]

The number of nucleoli in lymphocyte nuclei was compared in the peripheral blood of the Chernobyl liquidators and non-irradiated persons (control). The former was significantly distinguished from the latter (p < 0.01) by the parameter "the number of nucleoli in lymphocytes", mean numbers of nucleoli per nucleus in these being 1.18 and 1.12, respectively. The increased number of nucleoli in lymphocytes of the Chernobyl liquidators may be associated with cytogenetic radiation effects.     

Specific changes in auditory cognitive evoked potentials in those who participated in the liquidation of the Chernobyl accident: II. Analysis of the late P300 component

An integrated neuropsychological study and recording of auditory cognitive evoked potentials (EPs) using the three-stimulus oddball paradigm was performed in groups of ten subjects who participated in the liquidation of the consequences of the Chernobyl accident aged 50.5 ± 4.0 years and ten healthy subjects aged 47.0 ± 6.0 years. The neuropsychological study showed impairment of higher mental functions, including aspontaneity, fatigability, a decrease in the auditory-verbal and visual memories, and higher motor function deficiency, in cleanup workers (usually referred to as liquidators). Analysis of the amplitude and time characteristics of the P300 component of the auditory cognitive EP showed a decrease in the amplitude of this component in all cortical areas of liquidators in both experimental situations and for all stimuli compared to healthy subjects of the same age. Analysis of the latent period (LP) of P300 in liquidators showed the most distinct increase in the situation of passive audition for all types of stimuli. Analysis of the patterns of reactive rearrangements in different experimental situations showed that the P300 LPs of healthy subjects were similar for all types of stimuli during passive audition and were higher for the significant stimulus in the situation of counting. Liquidators were characterized by an type of response, with the LPs of responses to most stimuli increased in both experimental situations. Analysis of regional changes in the P300 LP showed that the differences in the P300 LP between the groups were the largest in the frontal areas of the left hemisphere. In addition, liquidators exhibited “uneconomical, excessive” responses as compared to normal responses, which suggests a decrease in the attention and memory capacities and could contribute to the impairment of higher mental functions. The changes in the amplitude and time characteristics of the P300 component of auditory EPs suggest deceleration of perception, processing, and analysis of information combined with weakened inhibition. The changes found in liquidators are similar to those observed in elderly people, which supports the hypotheses on accelerated brain aging and on pathological aging caused by low-dose irradiation.     

Microsatellite mutations show no increases in the children of the Chernobyl liquidators

We performed a study on Belarusian "liquidators", exploring whether increase in the frequencies of germline mutations at microsatellite loci could be found in their progeny. The liquidators, mostly young males, were those involved (during 1986 and 1987) in clean-up operations in the radioactively contaminated area following the Chernobyl nuclear power plant accident in 1986. Many liquidators fathered children during the clean-up period and after the work had been terminated. The numbers of families studied were 64 (liquidators) and 66 (controls). A total of 72 loci (31 autosomal, one X-linked and 40 Y-linked) were used. DNA was isolated from peripheral blood lymphocytes and the microsatellite loci were amplified by the polymerase chain reaction with fluorescence-labelled primers. Mutations were detected as variations in the length of the loci. At the Y-linked loci, the mutation rates (expressed as number of mutations among the total number of loci for the individuals included) are 2.9 x 10(-3) (4/1392) and 2.1 x 10(-3) (3/1458) in the children of exposed and control parents, respectively. This difference is not statistically significant. At the autosomal loci, the corresponding estimates are 5.9 x 10(-3) (11/1862; exposed group) and 8.5 x 10(-3) (18/2108; control). Again, the difference is not significant. The possibility that the Belarusian population might have been unexpectedly exposed to some chemical contaminants in the environment appears unlikely in view of the finding that the spontaneous mutation rates at the same set of loci in several non-Belarusian populations were similar to those in Belarus. The estimated mean radiation dose to the liquidators was small, being about 39 mSv, and this might be one reason why no increases in mutation rates due to radiation could be found.     

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.     

Determination of autoantibodies to antigens of thymic epithelial cells of clean up team workers and patients who survived acute radiation sickness at distant periods after irradiation]

A group of patients, suffering from sequelae of acute radiation sickness (ARS), and liquidators was studied 5 years after exposure to a complex of factors resulting from the Chernobyl A.P.S. disaster. Studied were: the antibody titres to antigens of the cytoplasm of thymus epithelial reticulum cells and to Hassall's corpuscles the levels of serum immunoglobulins M, G, A; and the content of serum alpha 1-thymosin. Patients with ARS sequelae and liquidators showed a high level and incidence of autoantibodies to antigens of cytoplasm of thymus epithelial reticulum cells and to Hassall's corpuscles. There were no significant differences between the antibody levels in the blood of patients with ARS sequelae and liquidators. The antibodies were found to belong to IgM class; there was a correlation between the serum IgM titres and the rate of the indirect immunofluorescence reaction with autoantibodies to antigens of the cytoplasm of the thymus epithelial reticulum cells. To identify autoantibodies cryostat sections of human and mouse, (CBA x C57BL/6) F1, thymus as well as the epithelial and stromal cell culture of mouse thymus can equally be used.     

An epidemiological analysis of monitoring of the immune status of chernobyl nuclear accident liquidators for early detection of risk groups and diagnosis of cancer diseases. Communication 1

Ionizing radiation is one of the major risk factors for cancer diseases. The question on the rate of malignant neoplasms (MNs) and their early detection in Chernobyl nuclear accident (ChNA) liquidators is still open. In this work, the results of a long-term immunological monitoring of the ChNA liquidators who live in the northwestern region of Russia have been analyzed with an attempt to detect the predictors of cancer in this population cohort. The rate of newly detected MN cases in the cohort of followup ChNA liquidators monitored in 1990–2009 was 8.856% (89 cases per 1005 persons), which is somewhat higher as compared with the average rate for the total population. As for the rate of individual MN types, lung, gastric, and prostate cancers were prevalent, which matches the worldwide trend in MN abundance. It was shown that 1-3 years before the MN diagnosis, liquidators displayed detectable changes in their immune status, including a decrease in the percentages of CD3⁺ and CD4⁺ T lymphocytes, and, to a lesser degree, B lymphocytes; a decrease in the CD4⁺/CD8⁺ ratio; increase in the relative and absolute contents of CD16⁺ lymphocytes; increase in the absolute CD8⁺ T lymphocyte counts; prevalence of CD3⁺16/56⁺ (NK-T) cells over CD3-16/56⁺ (NK) cells; and increase in the activity of phagocytes. The patients who displayed one or several of the listed characteristics should be ascribed to the MN risk group to be assessed for cancer markers, be more comprehensively examined, and be the subjects of dynamic observation.     

Cytogenetic effects in peripheral blood lymphocytes in descendants of chernobyl disaster liquidators under the impact of mitomycin c in vitro and folic acid in vivo

Data on cytogenetic examinations of the descendans of Chernobyl disaster liquidators (cleanup personnel) have been obtained. It has been established that the level of spontaneous chromosomal aberrations before folic acid administration was 1.8 times higher than that value after its employment (4.45 vs 2.42%, p < 0.01). In lymphocyte cultures treated with mitomycin C accompanied by folic acid, it was 4.5 times higher before their administration (23.95 vs 5.36%, p < 0.001). The data obtained confirm the possibility of stabilizing the genetic apparatus in the descendans of Chernobyl disaster liquidators after folic acid administration.     

Dynamics of immune status indices of liquidators in the remote period after the accident at the Chernobyl NPP

In the report there are present the results of monitoring of the state of immune status in the remote period after the accident at the Chernobyl Nuclear Power Plant among three groups of liquidators, which were from Moscow and the Moscow district, the Northwestern region of Leningrad district and from Krasnoyarsk territory. During the monitoring of the liquidators from different regions there was found phenotype of immune status with regional characteristics. In the Moscow district the clinical displays of immune insufficiency prevail and in the North western region the modifications of immune status prevail among liquidators. In all the groups we could see quantitative and immunoregulatory disbalance with the increase of parameters of cellular activity such as CD95+, HLA-DR+, T-activated lymphocytes, fluctuation cytotoxic cells (CD8+, CD16+), persevering disimmunoglobulinemia with differently directed modification serum of immunoglobulins at decrease B-lymphocytes. By the end of the twenty-year period after the accident we can see a similar phenotype of immune status in all the groups with increasing of the marker of late activation (HLA-DR+) and apoptotic activity (CD95+) and it is potentially dangerous regarding cancerogenesis. According to the basis of long-term monitoring there has been discovered the immune characteristic of proliferative syndrome for the first time. The monitoring of 2004 has revealed a huge similarity immune status at non-malignant growth at significant decrease CD25+ in the Northwestern region and some differences in common IgE.