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