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.

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.

Preconceptive irradiation is considered to be a potential risk factor that can cause hemolymphoblastosis in children conceived and borne by irradiated parents. A population cohort that comprises workers employed at "Mayak" Production Association (Mayak PA), the first nuclear cycle enterprise, is a unique sampling to calculate a carcinogenic risk in their children.Our research goal was to assess risk of hemolymphoblastosis among children conceived and borne by workers employed at Mayak PA with individual preconceptive accumulated absorbed dozes.Data and methods. We performed retrospective research as per "case-control" study among all the people living in the city of Ozersk located near Mayak PA. Hemolymphoblastosis diagnosed in people younger than 25 in 1949-2009 (81 people) were considered to be "cases"; "controls were chosen taking into account sex, birth date, and parents' age when a child was borne (324 people). We calculated odds ratio and excessive relative risk per external gamma-radiation dose unit (ERR/Gy) with 95 % confidence interval; to do that, we applied PEGAN program module of EPICURE software.Results. Acute leukemia prevailed in the structure of hemolymphoblastosis, acute lymphatic leukemia occupying the first place. We didn't reveal any statistic correlation between a factor related to parents' preconceptive irradiation and oncohematologic pathologies in their offspring: overall, odds relation was equal to 0.76 (0.46-1.26). As we analyzed "dose -effect" correlation, we didn't reveal any statistically significant increase in morbidity with hemolymphoblastosis depending on a dose of irradiation accumulated by their parents. ERR/Gy quotients were insignificant both for a dose accumulated by a mother and that accumulated by a father. Non-parametric analysis taking into account dose categories didn't reveal any elevated risks either.Conclusion. We didn't detect any dose dependence between long-term preconceptive external gamma-irradiation accumulated by parents and risks of hemolymphoblastosis in their children. However, a relatively insignificant number of hemolymphoblastosis cases among children younger than 25 imposes certain limitations on validity of our conclusions. Susceptibility to neoplasms in children and manifestation of the effect as a solid carcinoma at older ages are rather probable and it means that further observation and research is required.Key words: preconceptive radiation exposure of workers, children, dose dependence, risk assessment, malignant neoplasms in lymphoid and blood-making tissues.Read online __________________________  Sosnina S.

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