Association of methylation and transcriptional activity of redox system genes with apoptosis and necrosis of lymphocytes in chronically irradiated individuals

   Chronic radiation exposure can induce persistent epigenetic changes that affect the mechanisms of cell death and the development of long-term biological effects. The role of methylation of redox system genes in the regulation of apoptosis and necrosis of lymphocytes in chronically exposed individuals remains insufficiently studied.

   The aim of the study is to assess the association of promoter region methylation and transcriptional activity of redox system genes with the intensity of apoptosis and necrosis of peripheral blood lymphocytes in chronically exposed individuals.

   Materials and Methods: The study included 171 individuals: 99 persons exposed to chronic low-intensity radiation and 72 individuals from the comparison group who lived under similar social and living conditions. Apoptosis and necrosis of peripheral blood lymphocytes were assessed by flow cytometry. Molecular analysis included assessment of CpG dinucleotide methylation in the promoter regions of redox system genes and determination of their transcriptional activity.

   Results and Discussion: The level of lymphocyte necrosis was statistically significantly higher in the group of chronically exposed individuals compared with the comparison group (p = 0.033). Necrosis positively correlated with radiation doses to red bone marrow (ρ = 0.24; p = 0.001), thymus and peripheral lymphoid organs (ρ = 0.19; p = 0.013). Analysis of apoptosis revealed statistically significant positive correlations with methylation levels of SOD2 (ρ = 0.18; p = 0.017), GPX1 (ρ = 0.26; p = 0.001), GSTP1 (ρ = 0.22; p = 0.004), MPO (ρ = 0.41; p < 0.0001), and CAT (ρ = 0.21; p = 0.006). According to multiple regression analysis, apoptosis was associated with GSTP1 and MPO methylation.

   Conclusion: Thus, in chronically exposed individuals in the long-term period after exposure, necrotic lymphocyte death is predominantly associated with radiation dose, whereas apoptosis is associated with hypermethylation of promoter regions of redox system genes.

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