Chornobyl Cleanup Workers Research Articles

Смертність через провідні непухлинні хвороби учасників ліквідації наслідків аварії на ЧАЕС та мешканців радіоактивно забруднених територій у віддаленому періоді після аварії

The purpose of the study: Based on a descriptive analysis, to determine the post-accident changes in the level and structure of mortality of participants in the chornobyl cleanup workers of the accident at the Chornobyl Nuclear Power Plant (ULNA) and residents of RADIATION- contaminated TERRITORIES )residents of the RZT) of Ukraine from the main non-neoplastic diseases depending on age, time since the date of the accident and gender. Materials and methods: Mortality from non-neoplastic pathology in 1986-1987 in ULNA, numbering 64,762, and residents of RZT, numbering 174,860, aged 18-60 on the date of the accident as a result of the accident at the Chornobyl nuclear power plant, was studied based on clinical-epidemiological and dose data of the State Register of Ukraine. Epidemiological, medical-statistical, analytical methods were used during the research. Research results: On the basis of descriptive analysis, a description of the level and structure of mortality from non-neoplastic diseases of the ULNA and the residents of the RZT was provided, both for the entire post-accident period and for five-year periods. In ULNA, mortality increased with each five-year period and in recent years has increased by 15.7 times compared to the initial period. In residents of the radioactively contaminated territory of Ukraine, the mortality rate increased for 25 years after the accident, with the highest rate in the period 2008-2012, regardless of age, with subsequent stabilization of the indicators. The structure of mortality among participants of the ULNA and residents of the RZT throughout the entire observation period remains unchanged and almost does not differ from the general mortality trends of the population of Ukraine. Diseases of the circulatory system, digestive organs, and respiratory organs are stable in terms of the frequency of the causes of death. Age, sex, and temporal differentiation of mortality, differences in nosological causes among defined categories of victims of the consequences of the accident at the Chornobyl nuclear power plant were revealed. Conclusions: During the post-accident observation period (1988-2017), diseases of the circulatory system, digestive organs, and respiratory organs remained the main causes of mortality in ULNA in and among residents of RZT aged 18–60 on the date of the Chornobyl accident. The dynamics of mortality in ULNA was characterized by growth during the entire period of observation, in residents of RZT – growth over 25 years with subsequent stabilization. It is necessary to take into account during dispensation the revealed features of mortality of ULNA and RZT in order to develop comprehensive measures to reduce the mortality of this contingent.

Psychological distress 35 years after the Chornobyl accident in the Lithuanian clean-up workers

ABSTRACT The adverse effects on the health of the Chornobyl nuclear power plant accident clean-up workers have been reported previously. However, there is a lack of studies on the mental health of Chornobyl clean-up workers. The current study explored psychological distress in a sample of Lithuanian clean-up workers 35 years after the accident. In total, 107 Lithuanian Chornobyl clean-up workers (Mage = 62.5) and 107 controls were included in the study. The Hospital Anxiety and Depression Scale (HAD) was used for the assessment of anxiety and depression. The depression symptoms were significantly higher in the clean-up workers compared to the control group. The prevalence of severe depression symptoms was 23.4% and 4.7% in the Chornobyl clean-up workers and control groups, respectively. The risk for severe depression was associated with Chornobyl clean-up work (adjusted OR = 5.9). No differences in the anxiety symptoms were found between clean-up workers and controls. The study revealed the deteriorated mental health of the Lithuanian Chornobyl clean-up workers 35 years after the disaster – in particular, high levels of depression. Psychosocial support programmes for clean-up workers should be provided to mitigate the adverse effects of the disaster.

NEUROPHYSIOLOGICAL BASIS OF THE COMBINED EFFECTS OF ACUTE STRESS AND LOW DOSES OF IONIZING RADIATION ON HUMAN BRAIN.

to study the clinical and neurophysiological features in the Chornobyl clean-up workers with a verified chronic cerebrovascular disease/cerebral small vessels disease (SVD) exposed to low doses of ionizing radiation (IR), employees of the Chornobyl Nuclear Power Plant (SSE ChNPP), who were exposed to the stress factor of a full-scale war as a result of being held captive by the Russian military at their workplaces, and individuals of the non-irradiated comparison group.Design, object and methods. A cross-sectional clinical study with parallel external control groups. We studied and carried out an expert statistical analysis of the clinical and neurophysiological characteristics of 62 male subjects, from which three examination groups were formed: 1) a randomized sample from the Clinical Epidemiological Register (CER) of the State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine» (NRCRM) of 22 Chornobyl clean-up workers ('Chornobyl liquidators') in 1986-1990,examined during 2020-2021, aged 50-68 years at the time of examination (M ± SD: (58.1 ± 5.2) years) with a documented external radiation dose of 0.03-2.30 Sv; 2) 24 SSE ChNPP employees exposed to the stress factor impact of a full-scale war as a result of being held captive by the Russian military at their workplaces. The average age of the examined was (54.5 ± 5.8) years (range 46-71 years). 3) Comparison group - 16 non-exposed men with verified chronic cerebrovascular disease/cerebral small vessels disease (SVD). The average age of the examined was (57.8 ± 5.6) years (range 50-70 years). Neurophysiological studies confirm the presence of the pronounced dysfunction of the cortico-limbic system of the left dominant hemisphere of the brain with special involvement of the hippocampus in the Chornobyl clean-up workers. In the SSE ChNPP group, for the first time, the disorders of cerebral neurodynamics were detected in the form of functional hypofrontality and hyperfunction of the cortico-limbic system with lateralization to the right hemisphere. Today there exists a long-term thorough methodological and evidence base for a possible neurophysiological diagnosis and differential diagnosis of the combined cerebral effects of IR and psycho-emotional stress associated with the conditions of military conflicts. Neurophysiological technologies can be used in the objective professional and qualification selection of employees in a number of professions that require quick and responsible decision-making. Employees of SSE ChNPP need further medical and psychological support due to an increased risk of developing mental health disorders.

Schizophrenia spectrum disorders following past exposure to ionizing radiation and SARS CoV-2 infection

IntroductionWhether exist a potential association between schizophrenia spectrum disorders following past exposure to ionizing radiation and SARS CoV-2 infection is unknown.ObjectivesTo assess a possible role of double radiation-viral exposure in pre- and postnatal periods in schizophrenia spectrum disorders genesis.MethodsIntegration and analysis of information available with the results of own clinical and epidemiological studies.ResultsThe renaissance of interest to the viral hypothesis of schizophrenia is observing during the current COVID-19 pandemic. There is an increasing number of cases and case series reports on psychotic schizophreniform disorders following SARS CoV-2 infection diagnosed as COVID-19-asssociated brief psychotic disorder, first episode psychosis, acute and transient psychotic disorder. The prevalence rate of schizophrenia in A-bomb survivors in Nagasaki was very high – 6 % (Nakane and Ohta, 1986), and increased in those prenatally exposed to A-bombing (Imamura et al., 1995) and medical X-irradiation (Gross et al., 2018). We found a significant increase in the schizophrenia incidence in the Chornobyl exclusion zone personnel, as well as schizophreniform syndromes in Chornobyl clean-up workers (liquidators) irradiated by moderate to high doses (more than 0.30 Sv). The neural diathesis-stressor hypothesis of schizophrenia spectrum disorders was proposed (Loganovsky and Loganovskaja, 2000; Loganovsky et al., 2005). Recently we observed the clinical case of organic schizophrenia-like disorder in the liquidator who was ill with COVID-19.ConclusionsThe linkage between schizophrenia spectrum disorders following past exposure to ionizing radiation and SARS CoV-2 infection can exist that should be studied on the irradiated cohorts with following COVID-19.DisclosureNo significant relationships.

Impact of uncertainties in exposure assessment on thyroid cancer risk among cleanup workers in Ukraine exposed due to the Chornobyl accident.

A large excess risk of thyroid cancer was observed among Belarusian/Russian/Baltic Chornobyl cleanup workers. A more recent study of Ukraine cleanup workers found more modest excess risks of thyroid cancer. Dose errors in this data are substantial, associated with model uncertainties and questionnaire response. Regression calibration is often used for dose-error adjustment, but may not adequately account for the full error distribution. We aimed to examine the impact of exposure-assessment uncertainties on thyroid cancer among Ukrainian cleanup workers using Monte Carlo maximum likelihood, and compare with results derived using regression calibration. Analyses assessed the sensitivity of results to various components of internal and external dose. Regression calibration yielded an excess odds ratio per Gy (EOR/Gy) of 0.437 (95% CI -0.042, 1.577, p = 0.100), compared with the EOR/Gy using Monte Carlo maximum likelihood of 0.517 (95% CI -0.039, 2.035, p = 0.093). Trend risk estimates for follicular morphology tumors exhibited much more extreme effects of full-likelihood adjustment, the EOR/Gy using regression calibration of 3.224 (95% CI -0.082, 30.615, p = 0.068) becoming ~ 50% larger, 4.708 (95% CI -0.075, 85.143, p = 0.066) when using Monte Carlo maximum likelihood. Results were sensitive to omission of external components of dose. In summary, use of Monte Carlo maximum likelihood adjustment for dose error led to increases in trend risks, particularly for follicular morphology thyroid cancers, where risks increased by ~ 50%, and were borderline significant. The unexpected finding for follicular tumors needs to be replicated in other exposed groups.

Risk of thyroid cancer in Ukrainian cleanup workers following the Chornobyl accident.

Although much is known about the radiation-related risk of thyroid cancer in those exposed at young ages, less is known about the risk due to adult exposure, particularly in men. We aimed to examine the association between thyroid radiation dose received during adulthood and thyroid cancer risk in men. We conducted a nested case-control study (149 cases; 458 controls) of male, Ukrainian cleanup workers who first worked in the Chornobyl zone between ages 18 and 59years, with cases identified through linkage with the National Cancer Registry of Ukraine from 1988 to 2012. Individual thyroid doses due to external and internal exposure during the cleanup mission and during residence in contaminated settlements were estimated (total dose mean 199mGy; range 0.15mGy to 9.0Gy). The excess odds ratio per gray (EOR/Gy) for overall thyroid cancer was 0.40 (95% CI: - 0.05, 1.48; p-value = 0.118). Time since exposure was borderline significant (p-value = 0.061) in modifying this association so that less time since exposure was associated with a stronger EOR/Gy. An elevated, but nonsignificant association was observed for follicular thyroid cancer (EOR/Gy = 1.72; 95% CI: - 0.25, 13.69; p-value = 0.155) based on a small number of cases (n = 24). Our findings for radiation-related overall thyroid cancer risk are consistent with evidence of increased risks observed in most of the other studies of adult exposure, though the magnitude of the effect in this study is lower than in the previous case-control study of Chornobyl cleanup workers.

Estimation of radiation gonadal doses for the American–Ukrainian trio study of parental irradiation in Chornobyl cleanup workers and evacuees and germline mutations in their offspring

Radiation doses of parents exposed from the Chornobyl accident as cleanup workers or evacuees were estimated in the National Cancer Institute-National Research Center for Radiation Medicine trio (i.e. father, mother, offspring) study aimed at investigating the radiation effects on germline de novo mutations in children as well as other outcomes. Paternal (testes) and maternal (ovaries) gonadal doses were calculated along with associated uncertainty distributions for the following exposure pathways: (a) external irradiation during the cleanup mission, (b) external irradiation during residence in Pripyat, and (c) external irradiation and (d) ingestion of radiocesium isotopes, such as 134Cs and 137Cs, during residence in settlements other than Pripyat. Gonadal doses were reconstructed for 298 trios for the periods from the time of the accident on 26 April 1986 to two time points before the child’s date of birth (DOB): 51 (DOB-51) and 38 (DOB-38) weeks. The two doses, DOB-51 and DOB-38 were equal (within 1 mGy) in most instances, except for 35 fathers where the conception of the child occurred within 3 months of exposure or during exposure. The arithmetic mean of gonadal DOB-38 doses was 227 mGy (median: 11 mGy, range 0–4080 mGy) and 8.5 mGy (median: 1.0 mGy, range 0–550 mGy) for fathers and mothers, respectively. Gonadal doses varied considerably depending on the exposure pathway, the highest gonadal DOB-38 doses being received during the cleanup mission (mean doses of 376 and 34 mGy, median of 144 and 7.4 mGy for fathers and mothers, respectively), followed by exposure during residence in Pripyat (7.7 and 13 mGy for mean, 7.2 and 6.2 mGy for median doses) and during residence in other settlements (2.0 and 2.1 mGy for mean, 0.91 and 0.81 mGy for median doses). Monte Carlo simulations were used to estimate the parental gonadal doses and associated uncertainties. The geometric standard deviations (GSDs) in the individual parental stochastic doses due to external irradiation during the cleanup mission varied from 1.2 to 4.7 (mean of 1.8), while during residence in Pripyat they varied from 1.4 to 2.8 (mean of 1.8), while the mean GSD in doses received during residence in settlements other than Pripyat was 1.3 and 1.4 for external irradiation and ingestion of radiocesium isotopes, respectively.

СHARACTERISTICS OF CYCLIN D1-MEDIATED REGULATION OF CELL CYCLE OF PERIPHERAL BLOOD LIMPHOCYTES OF CHORNOBYL CLEAN-UP WORKERS AND PERSONS WITH MALIGNANT NEOPLASMS OF THE ORAL CAVITY, OROPHARYNX AND LARYNGOPHARYNX.

to explore proliferative potential of peripheral blood lymphocytes of Chornobyl clean-up workers and persons with malignant neoplasms of the oral cavity, oropharynx and laryngopharynx by level of expression of cyclin D1 and quantitative parameters of cell cycle. A total of 294 men aged (58.47 ± 7.32) were surveyed, 215 of them were Chornobyl clean"up workers (1986-1987), exposed at the dose range 10.43-3623.31 mSv; 49 persons of the control group and 30persons with malignant neoplasms of the oral cavity, oropharynx and laryngopharynx at III, IVА and IVВ stages ofthe disease. The analysis of parameters of cell cycle and proliferative activity of peripheral blood (PB) lymphocyteswas performed using the flow cytometry. The evaluation of distribution of cells by G0/G1, S, G2/M cell cycle phaseswas done in vivo and in in vitro. Proliferative potential was analyzed by level of expression of cytoplasmic protein ofcyclin D1. Proliferative potential of PB lymphocytes of Chornobyl clean"up workers and persons with malignant neo"plasms of the oral cavity, oropharynx and laryngopharynx was assessed. An increase in the level of spontaneousсyclin D1 expression and disturbance of сyclin D1-dependent regulation of cell cycle of PB lymphocytes after mito"gen activation were determined in the Chornobyl clean-up workers. An increase in pool of cells in the S" and G2/M"phases of cell cycle was detected, which characterizes high proliferative potential of PB lymphocytes. These changesare most pronounced in the subgroup of persons with a radiation dose of D > 500 mSv, and in persons with oncolo"gical pathology. A positive linear dependence has been established between the radiation dose and the number of cellsin the S"phase of cell cycle in the subgroup of Chornobyl clean"up workers with a radiation dose of D > 500 mSv. The detected changes of cyclin D1-dependent regulation of cell cycle and proliferative status of lymphocytes depend on the radiation dose, can be a manifestation of genome instability and be a cause for risks of oncogenesis, in a remote period after radiation exposure.

CHANGES IN GENE EXPRESSION ASSOCIATED WITH NON-CANCER EFFECTS OF THE CHORNOBYL CLEAN-UP WORKERS IN THE REMOTE PERIOD AFTER EXPOSURE.

to establish the connection of radiation-induced changes in gene expression with the realized pathology of the broncho-pulmonary and cardiovascular systems in Chornobyl clean-up workers. We examined 314 male Chornobyl clean-up workers (main group; age (58.94 ± 6.82) years(M ± SD); min 33, max 79 years; radiation dose (411.82 ± 625.41) mSv (M ± SD); min 1.74, max 3600 mSv) with various nosological forms of cardiovascular and broncho-pulmonary pathology (BPP) and 50 subjects of the controlgroup: age (50.50 ± 5.73) years (M ± SD); min 41, max 67 years. The relative level of BCL2, CDKN2A, CLSTN2, GSTM1,IFNG, IL1B, MCF2L, SERPINB9, STAT3, TERF1, TERF2, TERT, TNF, TP53, CCND1, CSF2, VEGFA genes expression was determined inperipheral blood leukocytes by real-time PCR (7900 HT Fast Real-Time PCR System (Applied Biosystems, USA)). The«gene-disease» association was determined on statistical models stratified separately for each disease and gene.Logistic regression was used to calculate the odds ratio. Increased GSTM1 gene expression and no changes in angiogenesis-related VEGFA gene expression werefound in the main group of patients with coronary heart disease (CHD). It was established overexpression of TP53,VEGF and IFNG genes in the group of patients with arterial hypertension (AH). At combination of these diseases anincrease of expression of СSF2, TERF1, TERF2 genes was established. The detected changes demonstrate an activationof the antioxidative defense system in patients with CHD, while AH is associated with the expression of genes ofangiogenesis and immune inflammation. It was shown an increase in the expression of genes associated with apoptosis and kinase activity (BCL2, CLSTN2, CDKN2), immune inflammation (CSF2, IL1B, TNF) in Chornobyl clean-upworkers with BPP. Expression of TP53 and GSTM1 (gene, associated with the glutathione system) was significantlyupregulated in the group of individuals with chronic bronchitis, whereas in patients with chronic obstructive pulmonary disease, no increase was detected; the expression of SERPINB9 and MCF2L genes was downregulated. Changes in the expression of genes, associated with the development of somatic pathology in theremote period after irradiation, in particular the genes of the immune response and inflammatory reactions CSF2,IFNG, IL1B, TNF; expression of genes that regulate cell proliferation, aging and apoptosis TP53, BCL2, MCF2L, CDKN2A,SERPINB9, TERF1, TERF2, TERT; genes that regulate cell adhesion and angiogenesis CLSTN2, VEGF.

DIFFUSION TENSOR MAGNETIC RESONANCE IMAGING IN EARLY DIAGNOSIS OF STRUCTURAL CHANGES IN BRAIN WHITE MATTER IN SMALL VESSEL DISEASE ASSOCIATED WITH ARTERIAL HYPERTENSION AND IONIZING RADIATION.

to determine the early signs of structural changes in brain white matter in small vessel disease associated with arterial hypertension and exposure to ionizing radiation using DTI-MRI. 45 patients (mean age (57.56 ± 6.34) years) with small vessel disease (SVD) associatedwith arterial hypertension (AH) were examined: group I - 20 patients, participants of liquidation of the accident atthe Chornobyl nuclear power plant (Chornobyl clean-up workers); group II - 25 patients not exposed to ionizingradiation. MRI was performed on an Ingenia 3T tomograph («Philips»). The fractional anisotropy (FA) was determined in the main associative and commissural pathways, periventricular prefrontal areas (fasciculus fronto-occipitalis superior / anterior - f. FO ant., corona radiata anterior - CR ant.) and semioval centers (SC). No signs of cerebral cortex or brain white matter (WM) atrophy, intracerebral microhemorrhages, and widespread areas of leukoaraiosis consolidation were observed in the examined patients. In the Chornobyl clean-up workers a larger number of foci of subcortical leukoaraiosis was visualized (80 %) on MRI images including multiple -8 (40 %), > 0.5 cm - 10 (50 %), with signs of consolidation - 5 (25 %). The results of the FA analysis in semiovalcenters showed its significant decrease in the patients of groups I and II (p < 0,007), regardless of the presence orabsence of visual signs of subcortical leukoaraiosis (ScLA) (III gr.: 253-317, p < 0.00001; IV gr.: 287- 375,p < 0.001). FA indicators in f. FO ant. and CR ant. in the patients of groups I and II differed insignificantly but weresubstantially lower than controls (p < 0.05). FA was significantly lower, compared to reference levels, in visuallyunchanged f. FO ant. (0.389-0.425; p = 0.015) and CR ant. (0.335-0.403; p = 0.05). In patients with AH-associated SVD of middle age, regardless of the effects of ionizing radiation, no significant changes in FA in the mainWM associative and commissural pathways were found (p > 0.05). DTI-MRI allows to detect early signs of structural changes in the white matter of the brain - a significant decrease in fractional anisotropy indicators in visually unchanged periventricular and subcortical areas. Themain associative and commissural pathways of the brain remain intact in the absence of widespread consolidatedfoci of leukoaraiosis and lacunar infarctions. The negative impact of ionizing radiation on the course of SVD associated with arterial hypertension is manifested by more active processes of WM disorganization: the prevalence andtendency to the consolidation of periventricular and subcortical leukoaraiosis foci, a significant FA decrease in semioval centers.

CHANGES OF CYCLIN D1-DEPENDENT REGULATION OF CELL CYCLE IN PERIPHERAL BLOOD LYMPHOCYTES OF CHORNOBYL CLEAN-UP WORKERS AT A REMOTE PERIOD AFTER RADIATION EXPOSURE.

To study proliferative potential of peripheral blood lymphocytes of Chornobyl clean-up workers by levelof expression of cyclin D1 and quantitative parameters of cell cycle at a remote period after radiation exposure. The research subject was the peripheral blood lymphocytes (PB) of Chornobyl clean-upworkers 30-33 years after radiation exposure. A total of 207 men were surveyed, 164 of them were clean-up workers exposed in the dose range 10.43-3623.31 mSv and 43 persons of the control group. Analysis of proliferationpotential (cell cycle initiation) and cyclin D1 expression in PB lymphocytes were performed in vitro by a micro methodof whole blood leukocytes culture with phytohemagglutinine-P (PHA). Sample preparation was performed by a standard immunofluorescent assay for intracellular proteins using the FITC labelled Mouse Anti-Human Cyclin D1Antibody Set. Cell distribution by cell cycle phases studied by propidium iodide DNA staining and analysis onFACSCalibur laser flow cytometer in histogram mode with separation of G0/G1-, S- and G2/M-regions and Sub-G0/G1-region (apoptotic cells). An increase in the level of spontaneous сyclin D1 expression and disturbance of сyclinD1-dependent regulation of cell cycle of PB lymphocytes after mitogen activation were determined in a remote period after radiation exposure. An increase in the level of cyclin D1 expression was accompanied by increase in pool ofcells in the S- and G2/M-phases of cell cycle which characterizes the high proliferative potential of PB lymphocytes.Mitogen-induced delay of cell cycle of lymphocytes in G1/S check point and reduction of S-phase was revealed.These changes are a manifestation of genomic instability caused by the effect of radiation and depend on the radiation dose. The results confirm the hypothesis about the significance of levels of cyclin D1 expression, as a criterion for manifestations of genome instability and risks of oncogenesis in a remote period after irradiation.

Level of Cyclin D1 protein in peripheral blood lymphocytes of Chornobyl clean-up workers in remote period after radiation exposure

Aim: to assess changes of products of Cyclin D1 protein in lymphocytes of peripheral blood of Chernobyl clean-up workers as remote results of the action of ionizing irradiation. Methods: there were examined 120 Chernobyl clean-up workers in the remote period after radiation exposure and 45 persons of the control group. For assessing mitogen-induced levels of Cyclin D1, the micro-method of cultivating erythrocytes of whole blood was used. The quantitative assessment of the spontaneous and mitogen-induced levels of Cyclin D1 in lymphocytes of peripheral blood (PB) was realized using the reagents FITC Mouse Anti-Human Cyclin D1 Antibody Set (BD, USA) by the method of flow cytometry.Research results: there was determined the dose-dependent increase of the spontaneous level of Cyclin D1 in PB lymphocytes of Chornobyl clean-up workers. High values of the parameter were established in the subgroup of Chornobyl clean-up workers, irradiated in the diapason of doses as 500-1000 mSv. Maximal values of Cyclin D1 level in PB lymphocytes were observed in Chornobyl clean-up workers at exacerbation of the bronchial-pulmonary pathology, bronchial asthma in anamnesis and in reconvalescents of acute radiation sickness with the radiation doses D ≥ 500 mSv. After mitogen stimulation of lymphocytes, there was noted the decrease of Cyclin D1 level in the group of Chornobyl clean-up workers and the increase in persons of the control group.Conclusions: the research revealed the differences in products of Cyclin D1 in PB lymphocytes of Chornobyl clean-up workers and persons of the control group. The revealed changes of the spontaneous and mitogen-induced levels of Cyclin D1 in PB lymphocytes of Chornobyl clean-up workers with the somatic pathology reflect disorders in regulation processes of proliferation and cellular cycle. The obtained data add ideas about mechanisms of the radiation-induced disorder of the cellular cycle that may be a manifestation of genome instability and become a trigger factor of carcinogenesis in the remote period after radiation exposure

Epidemiology of Late Health Effects in Ukrainian Chornobyl Cleanup Workers.

This article summarizes the results of 30 y of follow-up of cancer and noncancer effects in Ukrainian cleanup workers after the Chornobyl accident. The number of power plant employees and first responders with acute radiation syndrome under follow-up by the National Research Center for Radiation Medicine decreased from 179 in 1986-1991 to 105 in 2011-2015. Cancers and leukemia (19) and cardiovascular diseases (21) were the main causes of deaths among acute radiation syndrome survivors (54) during the postaccident period. Increased radiation risks of leukemia in the Ukrainian cohort of 110,645 cleanup workers exposed to low doses are comparable to those among survivors of the atomic bomb explosions in Japan in 1945. Additionally, an excess of chronic lymphocytic leukemia was demonstrated in the cleanup workers cohort for 26 y after the exposure. A significant excess of multiple myeloma incidence [standardized incidence rate (SIR) 1.61 %, 95% confidence interval (CI) 1.01-2.21], thyroid cancer (SIR 4.18, 95% CI 3.76-4.59), female breast cancer (SIR 1.57 CI 1.40-1.73), and all cancers combined (SIR 1.07; 95% CI 1.05-1.09) was registered. High prevalence was demonstrated for cardio- and cerebrovascular diseases and mental health changes. However, the reasons for the increases require further investigation. To monitor other possible late effects of radiation exposure in Chornobyl cleanup workers, analytical cohort and case-control studies need to include cardiovascular pathology, specifically types of potentially radiogenic cancers using a molecular epidemiology approach. Possible effects for further study include increased rates of thyroid, breast, and lung cancers and multiple myeloma; reduction of radiation risks of leukemia to population levels; and increased morbidity and mortality of cleanup workers from cardio- and cerebrovascular pathology.

Genomic characterization of chronic lymphocytic leukemia (CLL) in radiation-exposed Chornobyl cleanup workers

BackgroundChronic lymphocytic leukemia (CLL) was the predominant leukemia in a recent study of Chornobyl cleanup workers from Ukraine exposed to radiation (UR-CLL). Radiation risks of CLL significantly increased with increasing bone marrow radiation doses. Current analysis aimed to clarify whether the increased risks were due to radiation or to genetic mutations in the Ukrainian population.MethodsA detailed characterization of the genomic landscape was performed in a unique sample of 16 UR-CLL patients and age- and sex-matched unexposed general population Ukrainian-CLL (UN-CLL) and Western-CLL (W-CLL) patients (n = 28 and 100, respectively).ResultsMutations in telomere-maintenance pathway genes POT1 and ATM were more frequent in UR-CLL compared to UN-CLL and W-CLL (both p < 0.05). No significant enrichment in copy-number abnormalities at del13q14, del11q, del17p or trisomy12 was identified in UR-CLL compared to other groups. Type of work performed in the Chornobyl zone, age at exposure and at diagnosis, calendar time, and Rai stage were significant predictors of total genetic lesions (all p < 0.05). Tumor telomere length was significantly longer in UR-CLL than in UN-CLL (p = 0.009) and was associated with the POT1 mutation and survival.ConclusionsNo significant enrichment in copy-number abnormalities at CLL-associated genes was identified in UR-CLL compared to other groups. The novel associations between radiation exposure, telomere maintenance and CLL prognosis identified in this unique case series provide suggestive, though limited data and merit further investigation.

NEUROPSYCHOBIOLOGICAL MECHANISMS OF AFFECTIVE AND COGNITIVE DISORDERS IN THE CHORNOBYL CLEAN-UP WORKERS TAKING INTO ACCOUNT THE SPECIFIC GENE POLYMORPHISMS.

Relevance of the present work is determined by the considerable prevalence of both affective and cognitive disor-ders in the victims due to the Chornobyl accident, the pathogenesis of which is insufficiently studied.Objective is to identify the neuropsychiobiological mechanisms of the formation of the remote affective and cog-nitive disorders following exposure to ionizing radiation taking into account the specific gene polymorphisms.Design, object and methods of research. The retrospective and prospective cohort study with the external andinternal control groups. The randomized sample of the male participants in liquidation of the consequences of theaccident (Chornobyl clean-up workers, liquidators) at the Chornobyl nuclear power plant (ChNPP) in 1986-1987(n = 198) recruited from the Clinico-epidemiological registry (CER) of NRCRM aged 39-87 (M ± SD: 60.0-8.5 years)with the external irradiation dose ranged 0.6-5900.0 mSv (M ± SD: 456.0 ± 760.0 mSv) was examined. The compar-ison group (n = 110) consisted of the unexposed patients of the Radiation Psychoneurology Department with thecorresponding age and sex (the external control group). The internal control group included the liquidators irradi-ated at doses < 50.0 mSv (n = 42). The standard diagnostic neuropsychiatric scales, psychodiagnostic questionnairesand tests, neuropsychological methods (including the Wechsler Adult Intelligence Scale (WAIS) with premorbid IQ(pre-IQ) assessment), neuropsychiatric and psychophysiological methods (quantitative EEG (qEEG) and the audito-ry cognitive evoked potentials (Event-Related Potentials, ERP) were applied. The genotypes of the serotonin trans-porter gene SLC6A4 were determined by the 5_HTTLPR and rs25531 polymorphisms. The methods of descriptive and vari-ation statistics, non-parametric criteria, regression-correlation analysis, survival analysis by Kaplan - Meier and riskanalysis were used.Results. Cerebrovascular diseases, organic mental and depressive disorders, mainly of radiation-stress-relatednature, prevail among the liquidators. The overall risk of neuropsychiatric pathology increases (Pv < 0.001) with theirradiation dose. The verbal memory and learning are impaired, as well as the full IQ is reduced at the expense of theverbal one. The frequency of both mild cognitive impairment and dementia is risen. The cognitive impairment atdoses > 0.3 Sv is dose-dependent (r = 0.4-0.7; p = 0.03-0.003). Affective disorders (depression) and neurocogni-tive deficit are more severe at higher doses of irradiation (> 50 mSv). In the left posterior temporal region(Wernicke's area) the qEEG indices changes become dose-dependent at doses greater than 0.25-0.3 Sv. The dis-turbed brain information processes lateralized to the Wernicke's area are observed even at doses > 50 mSv. The car-riers of intermediate and low-level genotypes (LА/S, LА/LG, LG/LG, LG/S, S/S) of the serotonin transporter gene SLC6A4have more depressive disorders, especially severe ones, and tend to have more frequent and severe cognitive andstress-related disorders.The debut of depressive disorders in the carriers of the intermediate and low-activity genotypes occurs much earli-er (Log-Rank Test = 4.43, p = 0.035) in comparison with the carriers of the high-performance genotype LА/ LА.Conclusions. The radiation-induced dysfunction of the cortico-limbic system in the left dominant hemisphere ofthe human brain with a specific involvement of the hippocampus is considered to be the key cerebral basis of post-radiation organic brain damage. The association of genotypes by 5_HTTLPR and rs25531 polymorphisms of the SLC6A4gene with affective and cognitive disorders suggests the presence of neuropsychobiological features of these dis-orders associated with ionizing radiation depending on the certain gene polymorphisms.

RADIATION RISKS OF THYROID CANCER IN CHORNOBYL CLEAN-UP WORKERS USING THE ALTERNATIVE ESTIMATES OF DOSES OF EXTERNAL EXPOSURE.

The objective of this study was to estimate the thyroid cancer radiation risks - excess absolute risk(EAR), excess relative risk (ERR) and attributable fraction of risk (AR) in the cohort of 150,813 Ukrainian male clean-up workers during the 1986-2012 period (more than 25 years after the Chornobyl accident). The cohort under study of 150,813 Ukrainian men who participated emergency and clean-up work in 1986-1990 was formed based on the data of the Ukrainian State Register of persons affected due toChornobyl accident (SRU). The identification of thyroid cancer cases (216) was carried out by linking the SRU data-base with the National Cancer Registry of Ukraine (NCRU) data. Standardised incidence ratios (SIR) were estimatedcomparing thyroid cancer incidence in the cohort with the corresponding national indices. Excess absolute risk(EAR), excess relative risk (ERR) and attributable fraction of risk (AR) were calculated accounting for the alterna-tive dose estimates. The following sources of the average dose values for Ukrainian liquidators were used: officialtotal external dose records according to UNSCEAR 2008 report and results of external red bone marrow dose recon-struction by the RADRUE method for the cohort sample. For the radiation risk evaluation, these estimates were con-versed to the average external thyroid dose. Results of the long term study (1986-2012) of thyroid cancer risks in a cohort of 150813 Chornobyl clean-up workers («liquidators») from Ukraine are presented. Two options for the average thyroid dose estimates were usedfor radiation risks evaluation. According to the SRU and NCRU 216 incident thyroid cancers were diagnosed in 1986-2012 within the studied cohort with an overall SIR of 3.35 (95 % confidence interval (CI) 2.51-3.80). The SIR esti-mates were elevated throughout the entire follow-up period. Investigation of a contribution of the external expo-sure (according to the alternative values) showed the elevated dose associated thyroid cancer rates in the studiedcohort. Alternatively estimated EAR/104 PY Gy were of 1.86 (95 % CI 0.47-3.24) and 2.07 (95 % CI 0.53-3.62);ERR/Gy - 2.38 (95 % CI 0.60-4.15) and 2.66 (95 % CI 0.68-4.64) and AR % (Gy) 70.4 % and 72.7 % Gy. Obtained results prove the dose dependent increase of thyroid cancer incidence among UkrainianChornobyl clean-up workers. These conclusions are consistent with those received for combined cohort of Belarus,Russia and Baltic States liquidators.

VASCULAR PATHOLOGY OF AN EYE AND THE THREAT OF DEVELOPING AGE-RELATED MACULAR DEGENERATION AFTER RADIATION EXPOSURE

On the contrary to the previous expectations, the most common Chornobyl catastrophe victim’s pathology was the vascular pathology of an eye. The work is devoted to the assessment of changes in capillary tubes, arterioles and venules, which were irradiated as a result of Chornobyl catastrophe and those who have been exposed to radiation while working in the Chornobyl exclusion zone. The results of eye vascular system examination is presented by 615 persons: 358 Chornobyl clean-up workers, inspected in 1993–1994, 2007–2008 and 257 participants of works at the «Shelter» object, that were inspected in 2007–2008 and in 2017. Microcirculatory damages in conjunctiva are the most early ionizing radiation induced eye damage. Dose dependence from microcirculatory damages in conjunctiva has been proved. The conjunctiva index, which characterizes the evaluation degree of microcirculatory abnormalities value for individuals irradiated at a dose of up to 10 mSv was 5.33±0.34, at a dose of 10 to 30 mSv – 9.71±0.93. Thus, a significant (t=4.42, p&lt;0.05) increase in the display of microcirculatory abnormalities in conjunctiva was revealed with an increase in the dose load. In the correlation analysis, there was found a direct connection, r = 0.48, between the conjunctiva index and the dose of irradiation. The expressive tendency to correlate the negative dynamics of the macular zone with the degree of deterioration of microcirculation shows the effect of microcirculatory disorders on the development of age-related macular degeneration. At the correlation analysis, there was found a direct connection of significant decreased number of functioning capillaries with the deterioration of the macular zone of the retina (r=0.37). It is also advisable to appoint prophylactic complexes of lutein and zeoxanthine to patients in the case of microcirculatory disorders.

INCIDENCE OF MULTIPLE MYELOMA AMONG CLEANUP WORKERS OF THE CHORNOBYL ACCIDENT AND THEIR SURVIVAL

A study cohort consisted of 152,520 male cleanup workers resided in one of 6 regions of Ukraine or Kyiv city and registered in the Ukrainian State Chornobyl Registry (SChR). The Cohort Database was linked to the Ukrainian National Cancer Registry (NCR) Database to identify MM cases and to analyze MM incidence in 1996-2013. Standardized incidence ratios (SIR) for MM over the period 1996-2013 were calculated as compared to the general population of Ukraine. A 10-year lag period (when incident cases are not considered radiation-related) was applied. One-year and 5-year cause-specific survival of MM cases were calculated as percentage of those who were alive correspondingly for 1 or 5 years after diagnosis among overall diagnosed. By the moment, the 5-year survival rate either for the sub-period 2008-2013 or for the whole study period 1996-2013 cannot be determined. Vital status data were updated according to the recent SChR and NCR information. 75 MM cases diagnosed in 1986-2013 were identified in the studied cohort. 69 of them were included to the incidence analysis considering a 10-year lag period. While the incidence over 15 years after the accident did not differ significantly from the corresponding rate in general population of Ukraine, a tendency to increase was seen in the period from 16 to 21 years after the accident, and significantly increased SIR estimate was revealed for 2008-2013 (SIR 1.86, 95% confidence interval (CI) 1.27-2.44). The highest incidence was detected in 2008-2013 among cohort members diagnosed over the age of 50 years mostly due to the significant excess among those aged 60-69 (SIR 2.46, 95% CI 1.32-3.59). Survival rates in cleanup workers were shown to be higher than in the general population of Ukraine (73.9% and up to 65.0%, respectively). SIR for the 2008-2013 period, 22-27 years after the accident, demonstrated the significant excess of MM incidence among male cleanup workers. Survival of MM cases is higher in cleanup workers in comparison with that in general population. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

SPECIFIC INTERACTIONS BETWEEN LECTINS AND RED BLOOD CELLS OF CHORNOBYL CLEANUP WORKERS AS INDICATOR OF SOME LATE RADIATION EFFECTS

Growing interest in lectins is based on their diagnostic and pharmacological potential, especially the ability to inhibit proliferation and initiate apoptosis of cancer cells. In our research microplate lectinoassay able to detect carbohydrate containing structures (receptors) on erythrocyte surface have been proposed for Chornobyl cleanup workers (1986) monitoring. It was expected to reveal specific abnormalities associated with pathological condition arising as a result of late radiation effects. Red blood cell (RBC) specimens were taken from 171persons distributed into the six cohorts: nonexposed donors (1); chronically exposed to the doses below (2) and over 50cGy (3); exposed to acute radiation without (4) and with manifestation of acute radiation syndrome (5and 6). Lectins from 24species of medicinal plants were purified by ethanol fractionation and electrofocusing. Intensity of lectin-receptor interactions was determined in reaction of hemagglutination. Method of flow cytofluorometry was used to study B-cell counts. Hormone levels in blood serum were determined by radioimmunoassay. An elevated ability of RBC to interact with the panel of lectins was found in all cohorts of exposed persons versus nonexposed donors, moreover, changes in the intensity of lectin-receptor binding depended on the dose of irradiation. Diagnostic value of specific RBC reactions with some individual lectins has been elucidated. Elevated intensity of RBC reaction with Zea mays lectin was accompanied by a decrease in serum content of thyroid hormones T4and T3, as well as reduction of B-cell counts. In the case of Rubus caesius lectin the more intensive reaction with RBC, the higher level of hormone cortisol was observed. Deviations from donor's norm in intensity of lectin - RBC interactions in radiation exposed men are supposed to carry information about negative changes in their health status following Chornobyl catastrophe and show the diagnostic potential. The most sensitive reactions have been associated primarily with shifts in endocrine and immune systems. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

THE DISTRIBUTION OF TP53 GENE POLYMORPHISMS IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS, SUFFERERS OF CHORNOBYL NUCLEAR POWER PLANT ACCIDENT

The TP53 exonic and intronic SNPs were analyzed in 236 CLL patients by polymerase chain reaction and direct sequencing. The main group included 106 IR exposed CLL patients and thecontrol group was composed of 130 IR non-exposed CLL patients. Nineteen TP53 SNPs were found in the observed CLL cohort. No significant differences were found between the main and the control groups, but increased frequencies of T/T rs12947788 + G/G rs12951053 homozygotes and rs146340390 C/T variants were found among IR-exposed CLL patients compared with healthy Europeans (data from the 1000 Genomes Project). Rare nucleotide substitution rs146340390 (c.665C>T) was found only in the main group. These features were primarily typical for the most affected group of IR-exposed patients, namely, cleanup workers engaged in emergency works in the 2nd quarter of 1986. These preliminary findings don't contradict the assumption on possible influence of IR on CLL development via the p53-dependent pathway. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".