We studied the effect of technogenic radiation on the degree of promoter methylation in genes involved in apoptosis in blood lymphocytes of workers exposed to long-term γ-radiation during their professional activities. Blood samples for the analysis were obtained from 11 conventionally healthy men aged from 54 to 71 years (mean 66 years), workers of the Siberian Group of Chemical Enterprises working experience from 27 to 40 years (mean 30 years); the external exposure dose was 175.88 mSv (158.20-207.81 mSv). In all examined subjects, the degree of methylation of the promoters of apoptosis-related genes ranged from 0.22 to 50.00%. A correlation was found between the degree of methylation of BCLAF1 promoters (p=0.035) with the age of workers, BAX promoters (p=0.0289) with high content of aberrant cells, and APAF1 promoters (p=0.0152) with increased number of dicentric chromosomes. A relationship was found between the dose of external irradiation and the degree of methylation of gene promoters of BAD (p=0.0388), BID (р=0.0426), and HRK (р=0.0101) genes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Kuzmina NS, Myazin AE, Lapteva NSh, Rubanovich AV. Study of aberrant methylation in blood leukocytes of liquidators of the Chernobyl accident. Rad. Biol. Radioekol. 2014;54(2):127-139. doi: https://doi.org/10.7868/S0869803114020064. Russian.
Litvyakov NF, Freidin MB, Khalyuzova MV, Sazonov AE, Vasil’eva EO, Albakh EN, Isubakova DS, Blinov AP, Rodionova VI, Kut’ko AA, Karpov AB, Takhaurov RM. Frequency and spectrum of cytogenetic disorders in workers of the Siberian Group of Chemical Plants. Rad. Biol. Radioekol. 2014; 54(3):283-296. doi: https://doi.org/10.7868/S0869803114030084. Russian.
Behjati R, Kawai K, Inadome Y, Kano J, Akaza H, Noguchi M. APAF-1 is related to an undifferentiated state in the testicular germ cell tumor pathway. Cancer Sci. 2011;102(1):267-274. doi: https://doi.org/10.1111/j.1349-7006.2010.01750.x
Brown GT, Cash B, Alnabulsi A, Samuel LM, Murray GI. The expression and prognostic significance of bcl-2-associated transcription factor 1 in rectal cancer following neoadjuvant therapy. Histopathology. 2016;68(4):556-566. doi: https://doi.org/10.1111/his.12780
Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell. 2004;116(2):205-219. doi: https://doi.org/10.1016/s0092-8674(04)00046-7
Delia D, Mizutani S. The DNA damage response pathway in normal hematopoiesis and malignancies. Int. J. Hematol. 2017;106(3):328-334. doi: https://doi.org/10.1007/s12185-017-2300-7
Jain V, Das B. Global transcriptome profile reveals abundance of DNA damage response and repair genes in individuals from high level natural radiation areas of Kerala coast. PLoS One. 2017;12(11):e0187274. doi: https://doi.org/10.1371/journal.pone.0187274
Kuwana T, Mackey MR, Perkins G, Ellisman MH, Latterich M, Schneiter R, Green DR, Newmeyer DD. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell. 2002;111(3):331-342. doi: https://doi.org/10.1016/s0092-8674(02)01036-x
Maier P, Hartmann L, Wenz F, Herskind C. Cellular pathways in response to ionizing radiation and their targetability for tumor radiosensitization. Int. J. Mol. Sci. 2016;17(1):102. doi: https://doi.org/10.3390/ijms17010102
Manoochehri M, Karbasi A, Bandehpour M, Kazemi B. Down-regulation of BAX gene during carcinogenesis and acquisition of resistance to 5-FU in colorectal cancer. Pathol. Oncol. Res. 2014;20(2):301-307. doi: https://doi.org/10.1007/s12253-013-9695-0
Paul S, Amundson SA. Gene expression signatures of radiation exposure in peripheral white blood cells of smokers and non-smokers. Int. J. Radiat. Biol. 2011;87(8):791-801. doi: https://doi.org/10.3109/09553002.2011.568574
Toruno C, Carbonneau S, Stewart RA, Jette C. Interdependence of Bad and Puma during ionizing-radiation-induced apoptosis. PLoS One. 2014;9(2):e88151. doi: https://doi.org/10.1371/journal.pone.0088151
Xu M, Chen X, Chen N, Nie L, Li X, Li Q, Zeng H, Zhou Q. Synergistic silencing by promoter methylation and reduced AP-2alpha transactivation of the proapoptotic HRK gene confers apoptosis resistance and enhanced tumor growth. Am. J. Pathol. 2013;182(1):84-95. doi: https://doi.org/10.1016/j.ajpath.2012.09.018
Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell. 1995;80(2):285-291. doi: https://doi.org/10.1016/0092-8674(95)90411-5
Zhang Y, Chen H, Zhu H, Sun X. CBX8 promotes tumorigenesis and confers radioresistance in esophageal squamous cell carcinoma cells through targeting APAF1. Gene. 2019;711:143949. doi: https://doi.org/10.1016/j.gene.2019.143949
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 171, No. 3, pp. 339-343, March, 2021
Rights and permissions
About this article
Cite this article
Isubakova, D.S., Tsymbal, O.S., Bronikovskaya, E.V. et al. Methylation of Promoters of Apoptosis-Related Genes in Blood Lymphocytes of Workers Exposed to Occupational External Irradiation. Bull Exp Biol Med 171, 357–361 (2021). https://doi.org/10.1007/s10517-021-05227-y
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-021-05227-y