THE EPIGENETIC DISTURBANCES IN HUMAN BLOOD LEUKOCYTES IN
REMOTE PERIOD AFTER RADIATION EXPOSURE
Nina S. Kuzmina, Nellya Sh. Lapteva, Alexander B. Rubanovich
N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences,
Moscow, Russia
DNA methylation is a main epigenetic genomic modification, which not only
plays an important role in gene regulation but also is crucial for maintaining stability of
genome. The aberrant hypermethylation of cytosines in CpG islands (CGIs) associated
with active promoters is one of the main mechanisms of gene inactivation.
Methylation-sensitive PCR assay was used to analyze promoter
hypermethylation of p16/CDKN2A, p14/ARF, RASSF1A and GSTP1 genes in blood
leukocytes from 208 unirradiated volunteers and 124 irradiated subjects (83 Chernobyl
Nuclear Power Plant liquidators, 21 nuclear specialists, 20 residents of territories with
radioactive contamination, 4 persons evacuated in 1986 from the zone of Chernobyl
NPP). The age of unirradiated and irradiated subjects at the time of examination was
19 to 77 years and 24 to 77 years, respectively. Besides, 74 non-exposed offsprings (2.5
– 49 years) born from irradiated parents were examined. As a whole, a frequency of
individuals with promoter methylation of at least one of the analyzed genes in exposed
group is significantly higher compared to the control group (OR = 5.44, 95% CI = 2.62
- 11.76, p-value = 3,9 •10-7). No significant differences were found in the frequency of
children born to irradiated and unirradiated (control group) parents with the revealed
promoter hypermethylation of studied genes (power of the test is about 90%). On this
account, upon further analysis, the offsprings of irradiated individuals were assigned to
the control group. Multiple regression analysis showed that the growth in the number of
methylated loci of a set of RASSF1A and p14 genes is due to the age factor (β = 0.242;
p-value = 1.710-5). In contrast, the growth in the number of methylated loci of a set of
p16 and GSTP1 genes is exclusively due to the fact of radiation exposure (β = 0.290; pvalue = 1.710-7). Thus the reality of hypermethylation of CpG islands in gene
promoters is revealed in blood leukocytes in remote periods after irradiation of human
body. Differential role of age and radiation exposure factor in the hypermethylation of
various genes was identified.