Transcriptional activity of DNA-methyltransferase genes in the chronically exposed residents of the Ural region

About authors

1 Urals Research Center for Radiation Medicine of the Federal Medical Biological Agency, Chelyabinsk, Russia

2 Chelyabinsk State University, Chelyabinsk, Russia

Correspondence should be addressed: Vladislav S. Nikiforov
Vorovskogo, 68, korp. 1, Chelyabinsk, 454141, Russia; ur.liam@xvorofikin

About paper

Funding: the study was supported by the Federal Medical Biological Agency of Russia (Government contract № 27.501.21.2 of June, 11 2021).

Author contribution: Nikiforov VS — laboratory tests, statistical analysis, manuscript writing; Blinova EA, Akleyev AV— study planning, manuscript editing and preparing 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 FMBA of Russia (protocol № 3 dated June 28, 2022). The informed consent was submitted by all patients.

Received: 2022-06-29 Accepted: 2022-07-17 Published online: 2022-08-09

In addition to damaging the genetic apparatus of the cell, ionizing radiation can cause epigenetic alterations. DNA methylation that plays a vital part in regulation of cellular processes is a common epigenetic modification. DNA methylation ensured by DNA methyltransferases occurs in the CpG-rich sequences. The study was aimed to assess mRNA expression of genes encoding DNA methyltransferases (DNMT1, DNMT3A, DNMT3B) in the chronically exposed individuals who live along the River Techa over a long-term period. A total of 112 people were examined more than 65 years after the beginning of chronic exposure. The average accumulated dose to red bone marrow (RBM) was 782.0 ± 82.3 mGy, and the average accumulated dose to thymus and peripheral lymphoid organs was 93.2 ± 13.6 mGy. The subjects' age at the time of examination was 67.9 ± 0.8 years (54–83 years). The relative mRNA levels for the studied genes were assessed by realtime polymerase chain reaction (real-time PCR). mRNA expression of DNMT1 correlated positively with the dose to RBM (p = 0.04), thymus and peripheral lymphoid organs (p = 0.02), as well as with the dose rate in these organs (p = 0.05, p = 0.04, respectively) during the period of the highest levels of radiation exposure. In individuals exposed in the high dose range (over 1000 mGy) there was a significant increase in the expression of DNMT1 mRNA compared to the comparison group (p = 0.02). The findings may indicate the DNMT1 gene involvement in epigenetic alterations that occur in the chronically exposed people in the long term.

Keywords: gene expression, DNA methylation, low doses, chronic radiation exposure, Techa River