Effect of gene promoter methylation of apoptosis regulation on the intensity of lymphocyte cell death in exposed people

Apoptosis plays a vital role in maintaining the balance between proliferating cells and their death. Modifications in the methylation level of promoter regions of genes regulating cell death can affect the transcriptional activity of these genes and, consequently, the execution of apoptosis. At the same time, any defects in the implementation of the apoptotic pathway lead to the development of various diseases, including cancer. The objective of the study was to analyse the effect of methylation of promoter regions in BCL2, BAX, TP53 and MDM2 genes on the intensity of cell death of peripheral blood lymphocytes in individuals exposed to chronic low dose rate radiation. A total of 279 residents of the Techa riverside villages (Southern Urals) were examined, 145 of them were exposed to chronic low dose rate radiation due to the discharge of radioactive waste by the Mayak Production Association into the Techa River between 1949 and 1956 (the average accumulated dose to red bone marrow was 734 ± 49.40 mGy). Methylation of promoter regions of MDM2, TP53, BAX and BCL2 genes was analysed by methyl-sensitive realtime PCR. Apoptotic death of peripheral blood lymphocytes (PBLs) was studied by flow cytometry method. It was found that in the long-term period, after the onset of chronic radiation exposure, statistically significant differences were observed in the distribution of the examined people in the group of exposed people by the level of methylation of promoter regions of BCL2 and TP53 genes in comparison with unexposed people. When assessing the effect of methylation on the intensity of cell death in both the combined group and the group of exposed individuals, an increased frequency of PBLs at early and late stages of apoptosis is registered in the groups with hypomethylated MDM2 gene promoter.

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