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Epidemiological studies of late effects of preconceptional (prior to conception) radiation exposure are necessary in order to understand the risks of tumor and non-tumor pathology in next generations. Research of possible relation between parental preconceptional exposure and development of endocrine and metabolic disorders in the offspring is one of the topical issues of radiation hygiene. The objective of the study: comparative analysis of endocrine and metabolic pathology in children of the individuals exposed to long term preconceptional external gamma-radiation at the Mayak Production Association – at the first atomic industry facility on Russia. Materials and methods: A retrospective research was performed based on the Ozyorsk Children’s Health Registry. Ozyorsk – the city where Mayak Production Association is the enterprise forming the city. Analysis of endocrine and metabolic disorders was performed for 13880 children of 1949-1973 years of birth who were born and resided in Ozyorsk; parents of 9321 children of this number had accumulated doses of prolonged external gamma-radiation exposure at the production facility prior to conception. A comparative analysis of the structure and incidence of “Endocrine, nutritional and metabolic diseases” and nosological forms of this class of pathology was performed. Characteristic features of parental preconceptional exposure were analyzed in relation to thyroid pathology in children. Relative risk of endocrine and metabolic disorders among the children of exposed and unexposed parents was calculated for the whole disease class and for certain nosologies. Results: A significant predominance of thyroid diseases, particularly, iodine deficiencies, was detected at an earlier age among the offspring of Mayak Production Association workers compared to the control group; these cases were mostly related to low dose parental preconceptional exposure. Thyroid cancer was further detected in 0.16% (15/9321) of the studied cohort of the offspring of exposed parents with average manifestation age of 42.6. Relative risk of thyroid diseases was significantly higher among the exposed parents’ offspring compared to the controls: 2.0 among boys (95% confidence interval 1.38-2.9), 1.59 among girls (1.25-2.02) and in the group as a whole – 1.64 (1.34- 2.01). Relative risk of thyroid diseases related to iodine deficiency among the offspring of Mayak Production Association personnel was almost twice higher than the in the control group: 1.92 (1.3-2.84) among boys, 1.68 (1.29-2.2) among girls, 1.7 (1.36-2.12) in the whole group. Discussion and conclusion: A statistically significant overweight of non-tumor thyroid pathology in the offspring of Mayak Production Association personnel cannot be explained through external reasons taking into account similar climate and geographic conditions, possible technogenic exposure and the same unified medical survey of the followed children. We cannot exclude increased sensibility if thyroid tissue to iodine deficiency and its predisposition to hypertrophy and hyperplasia among the offspring of individuals exposed to long term occupational contact with ionizing radiation sources; that should be taken into account in the course of medical monitoring of these patients. Further research of transgenerational effects in the offspring of personnel of radiation hazardous production facilities are needed for complete understanding of the role of parental occupational exposure in health risks for further generations.

Cancer morbidity among patients examined using computed tomography within 10 years follow-up period depending on various factors has been retrospectively analyzed. Information on Ozyorsk residents examined at the Kasli District Hospital was retrospectively collected. The data collection period started in 2009 when the first computed tomography examination has been performed in the X-ray department of Kasli District Hospital, and ended by December 31, 2018. The data obtained in the study were linked to the local Cancer registry, the Death registry, and the “CT Registry” database to receive information about the vital status, cancer morbidity and CT examinations performed outside the Kasli District Hospital. Cumulative incidence has been accounted in terms of predisposed conditions associated with cancer, cancer diagnoses stated before the date of the first CT examination and CT-confirmed malignancy cases. As a result of the study, information on 275 examinations of 246 residents of the Ozyorsk urban district has been derived. By the end of the observation period, 46 cases of malignant tumors were accumulated in the study group. The average time from 1st CT to the end of follow-up was 6.5 years. The distribution of carcinogenic effects among patients examined using CT has been shown retrospectively from the date of birth to the date of the end of follow-up. The cumulative cancer incidence adjusted for predisposing conditions has been compared with the LSS data. No epidemiological data were found on the relationship between the detected cases of malignant tumors and the diagnostic radiation from CT scans. The data obtained in the study provide information on the long-term oncological effects among Ozyorsk residents examined using CT as a source of additional information for a comprehensive assessment of the low dose effects associated with diagnostic exposure in the Ozyorsk Computed Tomography Cohort study.

The results of a retrospective analysis of leukocytic indices and dynamics of peripheral blood values in relation to external gamma-exposure dose among the personnel of the first atomic production facility in Russia were presented. The study was performed on the basis of the database “Leukemia in the cohort of workers of the Mayak Production Association employed in 1948-1958”. The database contains hematological, clinical and dosimetry information on the two groups of workers: the study group includes individuals with leukemia as the cause of death (n=84); control group includes personnel without hematological cancer pathology (n=300). The control group was composed by selecting 3-4 internal control cases for each leukemia case taking into account gender, age of the start of the exposure and the same accumulated absorbed dose of gamma-exposure to red bone marrow. Based on 19592 analysis of peripheral blood we had described hematopoiesis shifts along cell lines, performed correlation analysis of interrelation between hemogram values and radiation dose, analyzed particular characteristics of blast cells’ appearance in peripheral blood flow in the period prior to leukemias. Comparative analysis of various leukocytic indices was performed among Mayak PA personnel for the first time. The diverse nature of the response of bone marrow hematopoiesis was noted; more pronounced hematological shifts were indicated regarding more intensive production exposure. A number of hematopoietic features were detected among people exposed to production radiation: 1) cytopenia in relation to minimum accumulated doses of radiation exposure in both studied groups; 2) more pronounced lability of hemograms in relation to increased accumulation dose of external gamma-exposure and period of radiation exposure among individuals who had developed leukemia in future in comparison to controls; 3) correlation between peripheral blood cells and accumulated doses of external gamma-exposure was characterized by the highest values of coefficients among individuals with future leukemias; 4) myeloblasts were most often registered among all the blast cells; proerythroblasts were characterized by the shortest average period from the start of the exposure and to the moment of their appearance in the peripheral blood flow (178 days in the study group); polychromatophile erythroblasts in peripheral blood were registered only among the workers with future leukemia; 5) when comparing leukocytic indices in proportion to the categories of accumulated doses of external gamma-exposure, a pronounced variability in the ratio of blood cells was observed among exposed individuals who were subsequently diagnosed with leukemia, especially in the range of 2.0-2.5 Gy. Thus, a comprehensive analysis of hematological parameters, including the assessment of leukocytic indices, is more informative than studying a standard hemogram. Particular features of the dynamics of the cellular composition of peripheral blood can be used as indicators of pathological hematopoiesis in exposed workers prior to clinical manifestation of leukemia.

A review of literature data regarding the heritable effects in offspring due to parents’ contact with mutagenic risk factors is presented. Studies on various factors of adverse effects on the hereditary apparatus, including chemical, infectious, physical and biological, are considered. The influence of smoking and parents’ age on the occurrence of de novo mutations is shown. Particular attention is paid to the review of publications on the role of the radiation factor in the genesis of hereditary disorders in offspring. Development stages of radiation genetics, the evolution of conception about radiation harm are described. The results of experimental, cytogenetic, molecular genetic, epidemiological studies analyzing the contribution of parental exposure to inherited pathology in progeny are presented. Special attention is paid to the “untargeted” effects of radiation and studies which prove the possibility of transgenerative transmission of genome instability are presented. The special contribution of studies on the cohort of atomic bomb victims offspring in Hiroshima and Nagasaki, which is considered as the main scientific platform for radiation risk assessment, is noted. There are articles about the offspring of persons who underwent therapeutic exposure, who had professional contact with ionizing radiation, who were exposed to radiation as a result of the Chernobyl accident, nuclear weapons tests at the Semipalatinsk test site, chronic radiation in the radioactively contaminated territory of the Techa river, areas with naturally increased radioactivity. As a result, it was noted that, despite numerous confirmations of radiation-induced effects in offspring obtained within experimental and molecular genetic studies, the results of epidemiological studies remain controversial. Possible reasons for these discrepancies are considered. An idea of views evolution regarding heritable effects in the international system of radiation safety is given. A new approach of the International Commission on Radiological Protection to heritable effects is described; the dynamics of tissue weighting factors for gonads in the assessment of effective radiation dose is shown. Methods for evaluating heritable effects are presented: the direct method and the doubling dose method. Attention is focused on the uncertainties that remain in the modern assessment of radiation genetic damage. The necessity of further study of radiation-induced heritable effects is shown. The perspective directions of studying the heritable effects are considered. The possibility of the analysis of heritable effects is described using the example of a cohort of the Mayak Production Association workers’ offspring – the country’s first nuclear industry enterprise.

A new analysis of lung cancer mortality in a cohort of male Mayak workers who started their employment in the plutonium and reprocessing plants between 1948 and 1958 has been carried out in terms of a relative risk model. The follow-up has been extended until 1999, moreover a new dosimetry system (DOSES2000) has been established. Particular emphasis has been given to a discrimination of the effects of external ?-exposure and internal a-exposure due to incorporated plutonium. This study has also utilized and incorporated the information from a cohort of Mayak reactor workers, who were exposed only externally to ?-rays. The influence of smoking as the main confounding factor for lung cancer has been studied. The baseline lung cancer mortality rate was not taken from national statistics but was derived from the cohort itself. The estimated excess relative risk for the plutonium a-rays was 0.23/Sv (95%CI: 0.16?0.31). The resulting risk coefficient for external ?-ray exposure was very low with a statistically insignificant estimate of 0.058/Sv (95%CI: -0.072?0.20). The inferred relative risk for smokers was 16.5 (95%CI: 12.6?20.5). [ABSTRACT FROM AUTHOR]