Effect of Methylation of Apoptosis Regulating Gene Promoters on the Lymphocyte Cell Death Rate in Exposed People

Apoptosis plays a vital role in maintaining the balance between cell proliferation and death. Aberrant methylation of the promoter regions of the genes that regulate cell death could influence their transcription activity, and, therefore, the execution of apoptosis. Defects in the apoptosis execution pathway result in the development of various diseases, including cancers. The objective of the current study is to analyze the effect of CpG-dinucleotide methylation in the promoter regions of BCL2, BAX, TP53, MDM2 genes on the cell death rate of peripheral blood lymphocytes (PBL) in people affected by chronic low dose-rate radiation exposure. In total 279 residents of the Techa riverside settlements (Southern Urals) were examined. Among them 145 individuals were affected by chronic low dose-rate radiation exposure due to the releases of radioactive waste into the Techa River by the Mayak Production Association over the period from 1949 through 1956 (mean accumulated dose to the red bone marrow of the examined people was 734 ± 49.40 mGy). The methylation in the promoter regions of MDM2, TP53, BAX, BCL2 genes was analyzed using the methylation-specific real-time PCR. The apoptotic death of PBL was studied using the flow cytometry method. It has been established that in the long-term period after the onset of chronic radiation exposure statistically significant differences were observed between the groups of exposed and unexposed people in the distribution of the examined individuals by the CpG-dinucleotide methylation level in the promoter regions of the BCL2 and TP53 genes. When the effect of methylation on the cell death rate was evaluated both in the combined group and separately in the group of exposed people, increase in the frequency of PBL at the early and late stage of apoptosis was registered in the groups with hypomethylated regions of the MDM2 gene promoter.