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Hypermethylation of CpG islands in the promoter regions of four genes (p53, ATM, SOD3, ESR1) was studied in blood leukocytes of irradiated humans (100 subjects: Chernobyl Nuclear Power Plant clean-up workers, nuclear specialists, residents of territories with radionuclide contamination) and 140 unirradiated subjects (control group) using methylation-sensitive polymerase chain reaction (PCR) assay. The obtained data significantly supplemented and allowed us to summarize results from several years of the study of radiation-induced hypermethylation in the gene promoters in various contingents of individuals exposed to chronic or fractionated radiation in a wide range of doses. The differential significance of age and radiation exposure in methylation of CpG islands in promoter regions of different genes was revealed, which is demonstrated by unidirectional effects observed in independent samples of irradiated individuals. The ROC curve analysis showed a high prognostic potential of consideration of detected epigenetic disorders as biomarkers of radiation exposure (AUC = 0.846 ± 0.015, p = 1.5E-48). Hypermethylation of the CpG islands in the RASSF1A and p14/ARF genes depends on age, and epigenetic modification of the p16/INK4A and GSTP1 loci is highly significantly associated with radiation exposure, which was verified on two test samples of the examined individuals. The revealed dose-dependent hypermethylation of the studied genes is indirectly confirmed by a positive associative relationship between the level of chromosomal aberrations and the frequency of methylated loci (r = 0.604, p = 2.3E-11). [ABSTRACT FROM AUTHOR]

The estimation of hypermethylation of the cell cycle (RASSF1A, p16/INK4A, p14/ARF) and detoxification (GSTP1) gene promoters was carried out in blood leukocytes of humans exposed to radiation as a result of the Chernobyl accident (98 individuals: accident liquidators, 76 individuals; adult residents of the territories with radionuclide contamination, 135–688 kBq/m2, 22 individuals) depending on their cytogenetic status. The results of multiple regression analysis ("Frequency of aberrations ~ age + number of hypermethylated genes") indicate a correlation of the total level of chromosomal type aberrations with the considered epigenetic disturbances (β = 0.256; р = 0.011), but not with age (β = –0.138; p = 0.165). The frequency of these cytogenetic disorders increases with an increase in the number of methylated loci. Thus, a positive association between the damages to the genome induced by radiation exposure in the range of small and medium doses (long time ago) and hypermethylation of promoters of the genes of the main protective systems of the cells was detected. [ABSTRACT FROM AUTHOR]