BCL-2, CDKN1A and ATM gene methylation in chronically exposed individuals
https://doi.org/10.47183/mes.2021.028
Abstract
DNA methylation is the most common epigenetic modification, caused by ionizing radiation. There may be both hypermethylation, which suppresses transcription of gene promoter regions, and hypomethylation, resulting in gene activation. Both mechanisms may be involved in carcinogenesis. The study was aimed to assess methylation status of CpG islands in the protective system BCL-2, CDKN1A and ATM gene promoters in the peripheral blood cells of the chronically exposed individuals, living in the villages, located along the Techa River, over a long-term period. Methylation of BCL-2, CDKN1A and ATM gene promoter regions in 68 residents of the villages, located along the Techa River (Chelyabinsk region), was assessed by the real-time methylation-specific PCR. The group of exposed individuals included 54 people with accumulated dose to red bone marrow within the range of 0.09–3.51 Gy. The comparison group included 14 people, living in similar economic and social environment, with the dose to red bone marrow, accumulated during the whole life, not exceeding 70 mGy. The pilot study of exposed individuals over a long period of time after chronic low-dose radiation exposure revealed no significant changes in methylation levels of CpG islands in the CDKN1A, BCL-2, ATM gene promoter regions compared to the comparison group. None were revealed in the dose subgroups “87–994 mGy” and “over 1000 mGy”.
Keywords
DNA methylation,
CpG islands,
long-term effects of exposure,
chronic exposure,
methylation-specific PCR
Supporting agencies: The study was carried out within the framework of the State assignment of Russian Federal Medical Biological Agency “Human Cell-Mediated Immunity During Realization of Chronic Radiation Exposure Late Effects” (code 27.002.20.800).
About the Authors
E. A. Blinova
Urals Research Center for Radiation Medicine of the Federal Medical Biological Agency; Chelyabinsk State University
Russian Federation
Russian Federation
Evgeniya A. Blinova
Vorovskogo, 68, korp. 1, Chelyabinsk, 454141
V. S. Nikiforov
Urals Research Center for Radiation Medicine of the Federal Medical Biological Agency; Chelyabinsk State University
Russian Federation
Russian Federation
Vorovskogo, 68, korp. 1, Chelyabinsk, 454141
M. A. Yanishevskaya
Urals Research Center for Radiation Medicine of the Federal Medical Biological Agency
Russian Federation
Russian Federation
Vorovskogo, 68, korp. 1, Chelyabinsk, 454141
A. V. Akleyev
Urals Research Center for Radiation Medicine of the Federal Medical Biological Agency; Chelyabinsk State University
Russian Federation
Russian Federation
Vorovskogo, 68, korp. 1, Chelyabinsk, 454141
References
1. Spainhour JC, Lim HS, Yi SV, Qiu P. Correlation patterns between DNA methylation and gene expression in the Cancer Genome Atlas. Cancer Inform. 2019; (18): 1–11. DOI: 10.1177/1176935119828776. PMID: 30792573. PMCID: PMC6376553.
2. Greenberg MVC, Bourchis D. The diverse roles of DNA methylation in mammalian development and disease. Nat Rev Mol Cell Biol. 2019; (20): 590–607. DOI: 10.1038/s41580-019-0159-6. PMID: 31399642.
3. Van Tongelen A, Loriot A, De Smet C. Oncogenic roles of DNA hypomethylation through the activation of cancer-germline genes. Cancer Lett. 2017; 28 (396): 130–7. DOI: 10.1016/j.canlet.2017.03.029. PMID: 28342986.
4. Edwards JR, Yarychkivska O, Boulard M, Bestor TH. DNA methylation and DNA methyltransferases. Epigenetics & Chromatin. 2017; 10 (23): 1–10. DOI: 10.1186/s13072-017-0130-8.
5. Kovalchuk O, Burke P, Besplug J, Slovack M, Filkowski J, Pogridny I. Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low dose X-ray irradiation. Mutat Res. 2004; 548 (1–2): 75–84. DOI: 10.1016/j.mrfmmm.2003.12.016. PMID: 15063138.
6. Kuzmina NS. Izuchenie aberrantnogo metilirovanija v lejkocitah krovi likvidatorov avarii na ChAJeS. Radiacionnaja biologija. Radiojekologija. 2014; 54 (2): 127–39. Russian.
7. Cho YH, Jang Y, Woo HD, Kim YJ, Kim SY, Christensen S, et al. LINE-1 Hypomethylation is associated with radiation-induced genomic instability in industrial radiographers. Environ Mol Mutagen. 2018; 60 (2): 174–84. DOI: 10.1002/em.22237.
8. Isubakova DS, Cymbal OS, Bronikovskaja EV, Litvjakov NV, Milto IV, Tahauov RM. Metilirovanie promotorov genov apoptoza v limfocitah krovi rabotnikov, podvergavshihsja v processe professional'noj dejatel'nosti dolgovremennomu vneshnemu oblucheniju. Bjulleten' jeksperimental'noj biologii i mediciny. 2021; 171 (3); 339–43. Russian.
9. Nikiforov VS, Blinova EA, Akleev AV. Vlijanie kompleksa faktorov radiacionnoj i neradiacionnoj prirody na profil' transkripcionnoj aktivnosti genov u lic, podvergshihsja hronicheskomu radiacionnomu vozdejstviju. Voprosy radiacionnoj bezopasnosti. 2019; 2 (94): 64–70. Russian.
10. Degteva MO, Napier BA, Tolstykh EI, Shiskina EA, Bougrov NG, Krestinina LYu, Akleev AV. Individual dose distribution in cohort of people exposed as a result of radioactive contamination of the Techa River. Medical Radiology and Radiation Safety. 2019; 64 (3): 46–53. DOI: 10.12737/article_5cf2364cb49523.98590475.
11. Kulis M, Esteller M. DNA methylation and cancer. Adv Genet. 2010; (70): 27–56. DOI: 10.1016/B978-0-12-380866-0.60002-2. PMID: 20920744.
12. Jaenisch R. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003; (33): 245–54. DOI: 10.1038/ng1089. PMID: 12610534.
13. Kuzmina NS, Lapteva NSh, Rubanovich AB. Hypermethylation of gene promoters in peripheral blood leukocytes in humans long term after radiation exposure. Environ Res. 2016; (146): 10–17. DOI: 10.1016/j.envres.2015.12.008.
Review
For citations:
Blinova E.A., Nikiforov V.S., Yanishevskaya M.A., Akleyev A.V. BCL-2, CDKN1A and ATM gene methylation in chronically exposed individuals. Extreme Medicine. 2021;23(3):11-15. https://doi.org/10.47183/mes.2021.028
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