Assessment of the Degree Of DNA Methylation in Lymphocytes аfter а Single Blood Irradiation in vitro

Abstract

DNA methylation is one of the processes of epigenetic regulation of the genome, which is sensitive to the influence of endogenous and exogenous factors. The effect of ionizing radiation on the genome is accompanied by a change in the degree of DNA methylation, which can be dose-dependent and persist for a long time after radiation exposure. The objective of the study was to assess the degree of DNA methylation of blood lymphocytes after a single exposure to gamma radiation at a dose of 1.5 Gy using wide-genome bisulfite sequencing. The study included 10 conditionally healthy male employees of the ionizing radiation facility who were not exposed to radiation and did not suffer from chronic diseases. The material was whole blood: 0 Gy (control samples) and 1.5 Gy (experimental samples irradiated with gamma radiation). After irradiation with subsequent cultivation of whole blood, DNA isolation and bisulfite sequencing of limited sets of genomic loci (Reduced representation bisulfite sequencing) was performed using XmaI restriction enzyme (XmaI-RRBS). 41 genes were identified, including 26 genes (HOXD4, PADI2, FOXK1, FTCD, PRDM16, TOM1, PPP1R14A, FLNB, OR1F1, RARA, CRTAC1, AP5B1, ARL5C, NOC2L, MAMDC4, FGFRL1, PPFIA3, CUX2, ANKRD20A19P, FAM83H-AS1, CBFA2T3, POLN, MIR4458HG, FNBP1, SPIRE2, and ZSCAN10) have a tendency to hypomethylation DNA, and another 15 genes (CHRNA4, SEPTIN9, ZNF174, ELK3, NFAM1, ALG10, SOX8, KLHL30, URI1, HBZ, KLF14, MYO16, MYEOV, DMKN, and PAX7) tend to have hypermethylated state detected in at least 50٪ of the experimental samples. Thus, the genes identified in this study can be promising markers of radiation exposure and, in the future, be used to develop a new type of biological dosimetry – epigenomic dosimetry of personnel in contact with ionizing radiation sources in the course of their professional activities.