Archives2018Vol. 58, No. 6pp. 581-588

Article

Dose Dependence of Hypermethylation of Gene Promoters in Blood Leukocytesin Humans Occupationally Exposed to External γ-Radiation

Kuzmina N.S.1, Lapteva N. Sh.1, Rusinova G.G.2, Azizova T.V.2, Vyazovskaya N.S.2, Rubanovich A.V.1

1 N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia. 2Southern Ural Biophysics Institute, Ozyorsk, Russia

Abstract

The study of promoter hypermethylation of a cell cycle (RASSF1A, p16/INK4A, p14/ARF, p53, АТМ), xenobiotic detoxification (GSTP1), antioxidant defense (SOD3) and estrogen receptor (ESR1) genes in blood leukocytes of 88 nuclear industry workers from the «Mayak» facility (53–86 years old at sampling), and 50 unirradiated subjects matched by age (control group) was carried out. «Mayak» workers were occupationally exposed to external γ-radiation. Accumulated doses to RBM (red bone marrow) ranged from 0.20 to 2.95 Gy. The time between the end of work with radiation and blood sampling was on average 15.95 ± 1.22 years. The trend towards dependence of promoter hypermethylation of p14/ARF and RASSFA on age rather than radiation exposure (logistic regression: p = 0.072) confirms previous results. The frequency of individuals displaying promoter methylation of at least one of the 6 genes (p16/INK4A, GSTP1, р53, АТМ, SOD3, ESR1) was significantly higher in the exposed group (62.5%) as compared to the control group (34%): p = 0.001, OR = = 3.24, 95% CI 1.56–6.69. A significantly elevated frequency of individuals with hypermethylated СpG islands in GSTP1 and SOD3 promoters was revealed among exposed subjects as compared to the control group (p = 0.014 and p = 0.021 respectively). A statistically significant association between the cumulative dose and the number of methylated promoters was revealed (r = 0.304, р = 3.2 × 10–4). Thus, the dose-dependent hypermethylation of CpG islands in gene promoters that is revealed in blood leukocytes long term after external exposure to γ-radiation was found.

Keywords

hypermethylation, CpG island, human leukocytes, external exposure to γ-radiation

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