Relationship between methylation of promoters of apoptosis genes in blood lymphocytes with the frequency of chromosomal aberrations and the dose of radiation

Abstract

BACKGROUND: Impaired apoptosis can have serious consequences: the accumulation of mutant cells, the development of teratogenic effects and malignant neoplasms. In this regard, the study of the mechanisms of changes in the activity of apoptosis due to methylation under the influence of long-term irradiation is urgent.

AIM: The study of the degree of methylation of gene promoters involved in the induction of apoptosis in the personnel of the Siberian Chemical Plant, exposed to long-term technogenic irradiation of ionizing radiation in the course of their professional activities.

MATERIALS AND METHODS: The study was performed on peripheral blood samples of employees of the Siberian Chemical Plant, with a total dose of external exposure from 100 to 300 mSv. Chromosomal aberrations were detected by standard karyotyping of cultured blood lymphocytes. The degree of gene promoters methylation was determined using MethylScreen technology.

RESULTS: The degree of gene methylation BIRC2, CASP3, CASP9, CIDEB, CRADD, DAPK1, DFFA, FADD, GADD45A, LTBR, TNFRSF21, TNFRSF25 ranges from 0.31 to 41.75%. A strong negative correlation was found between the degree of methylation of GADD45A (r = –0.7364, р = 0.009) with an increased frequency of aberrant cells, moderate negative correlation GADD45A (r = –0.6347, р = 0.035) with an increased frequency of dicentric chromosomes, moderate negative correlation CASP9 (r = –0.6606, р = 0.026), and strong negative correlation CIDEB (r = –0.7982, р = 0.003) with an increased frequency of chromatid fragments. A moderate negative correlation of the methylation degree of CASP9 (r = –0.6636, р = 0.026), and CIDEB (r = –0.6636, р = 0.026) with the total dose of external exposure was shown.

CONCLUSIONS: The decrease in the level of apoptosis at doses of 100–300 mSv can be explained by the achievement of the demethylation threshold for the promoters of the proapoptotic genes GADD45A, CASP9, CIDEB. This once again testifies in favor of the threshold model of the dependence of the radiation effect on the radiation dose.

Keywords

DNA methylation / chromosomal aberrations / ionizing radiation / promoter / apoptosis

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