Cytogenetic Disorders Depending on Hypermethylation of Gene Promoters in Exposed Individuals: Final Research Results

The results of study of hypermethylation of promoters of the cell cycle genes (RASSF1A, p16/INK4A, p14/ARF, p53, ATM), antioxidant protection (GSTP1, SOD3), and estrogen receptor (ESR1) are summarized in individuals exposed to chronic or fractionated irradiation in the range of small and medium doses (101 people, 24–78 years old, liquidators of the accident at the Chernobyl nuclear power plant, and adult residents of territories contaminated with radionuclides at 135–688 kBq/m2), in the aspect of the relationship of these epigenetic modifications with the cytogenetic status of the individual. Multiple regression analysis showed that the frequency of both simple and complex exchange aberrations of the chromosomal type is associated with the methylation status of the complex of the studied genes (β = 0.504, p = 1.9E-7 and β = 0.349, p = 3.6E-4, respectively), but not with age (β = –0.122, p = 0.178 and β = 0.153, p = 0.109). In general, highly significant differences were demonstrated between groups of exposed individuals with different epigenetic status (number of hypermethylated genes) for all cytogenetic parameters considered, with the exception of chromatid-type aberrations (Kruskal–Wallis test: p = 2E-4 and p = 5E-8 for the total frequency of cytogenetic disorders and rearrangements of the chromosomal type, respectively). The level of cytogenetic disorders of the chromosomal type increases with an increase in the number of methylated genes in irradiated individuals. The data obtained may point to general patterns in the mechanisms of induction and preservation over the years of the considered genetic and epigenetic effects of radiation.