The study of aberrant methylation in blood leukocytes of liquidators of the Chernobyl accident

: The study of aberrant methylation of CpG islands in the promoter regions of genes (P16/CDKN2A, P14/ARF, RASSF1A, GSTP1) in blood leukocytes of liquidators of the Chernobyl accident (n = 83, 38-76 years of age) and control subjects of two groups (n = 48, age ≤ 35 and n = 65, age > 35) was carried out using methylation-sensitive restriction endonuclease analysis followed by PCR. The total number of AciI sites in the analyzed fragments ranged from 2 to 7 for different genes. Only 1 subject (2.1%) from the control group (healthy young individuals, age ≤ 35) has methylation of the studied CpG--dinucleotides of RASSF1A gene. Promoter methylation of at least one of the genes analyzed was observed in 28.92% liquidators and significantly exceeded (p = 0.016) such rate in a one-age (> 35 years of age) control group (12.31%). A significantly elevated frequency (p = 0.023) of individuals with abnormal methylation of GSTP1 gene in the group of liquidators as compared to the control group was revealed. The occurrence of promoter methylation of RASSF1A gene significantly correlated with aging both in the control group (r = 0.214; p = 0.023) and in the liquidators of the Chernobyl accident (r = 0.230; p = 0.036). No similar trend was found for other genes. Multiple regression analysis showed that the growth in the number of methylated loci of a set of genes p16, p14 and GSTP1 is exclusively due to the fact of exposure (OR = 7.32, 95% CI = 2.49-25.83, p-value = 2.7 x 10(-5)). The results obtained demonstrate for the first time the reality of the radiation-induced aberrant methylation of CpG islands in promoters of genes involved in the basic protective, functions of cells in the human body in remote periods after radiation exposure.