ORIGINAL RESEARCH
Methylation of cell cycle and apoptosis genes’ promoters in exposed individuals with subsequent malignant neoplasms
1 Urals Research Center for Radiation Medicine, Chelyabinsk, Russia
2 Chelyabinsk State University, Chelyabinsk, Russia
Correspondence should be addressed: Eugenia A. Blinova
Vorovskogo, 68A, Chelyabinsk, 454141, Russia; ur.mrcru@avonilb
Acknowledgements: the article was prepared in the context of the Federal Target Program "Modernization of high-tech methods of identification of medical consequences of exposure to radiation of personnel of the Mayak Production Association and population of the Ural region," Contract № 27.501.21.2 of 11.06.2021.
Author contributions: E.A. Blinova — study planning, generalization of primary material, analysis and discussion of the results, article drafting; A.V. Korechenkova — laboratory tests, article drafting; V.S. Nikiforov — laboratory tests, article drafting; A.V. Akleyev — study planning, article editing, authoring of the final version of the article.
Compliance with ethical standards: the study was approved by the Ethics Committee of the Urals Research Center for Radiation Medicine of the FMBA of Russia (Minutes #2 of July 20, 2021). All participants signed the informed consent form to participate in the study.
DNA methylation plays an important role in carcinogenesis; there are many studies that investigate the degree of methylation of the entire genome, gene promoters, and non-coding elements in cancer cells, but much less information about changes of the methylation patterns in blood cells and links with the development of malignant neoplasms (MN). This study aimed to investigate the degree of methylation of promoter regions of cell cycle control and apoptosis genes (BAX, MDM2, TP53, NFkB1) in peripheral blood cells of persons chronically exposed to radiation with MN developing latently. The study included 200 persons chronically exposed to radiation from the Techa River, contaminated with nuclear wastes dumped into it. The level of methylation was assessed by real-time PCR. The participants were divided into exposed and control groups; comparing them, we found that in the former, the distribution of exposed individuals with latent MN by the degree of methylation of promoter regions of BAX, MDM2 and NFkB1 genes was significantly different from that in the latter (p < 0.001; p < 0.001; p = 0.004, respectively). It was established that, compared to the control group, the share of the test group participants with subsequent MN who had up to 10% of the BAX gene promoter regions methylated was significantly higher, and amounted to 98%, while in the control group this figure did not exceed 73% (p < 0.00001).
Keywords: carcinogenesis, chronic radiation exposure, the Techa River, gene methylation, CpG dinucleotides