Promoter methylation in key DNA damage response genes shows a positive correlation with cumulative dose in chronically low-dose radiation-exposed individuals

This pilot study investigated promoter DNA methylation in key DNA damage response (DDR) genes in individuals chronically exposed to low-dose ionizing radiation (LDIR) in Kerala, India. 26 healthy male residents of Kerala’s high level natural radiation areas (HLNRA) were selected and stratified based on lifetime cumulative radiation dose (100 mSv, n = 16). Promoter methylation of 16 DDR-related genes was assessed using Methylation Sensitive High resolution Melting (MS-HRM), with LINE-1 as a surrogate for global methylation. Gene expression of selected targets was measured by RT-qPCR. Global DNA methylation showed no significant difference across exposure groups. In contrast, promoters of RAD23B, DNMT3A, MRE11A, and BRCA1 were significantly hypermethylated in individuals with cumulative dose >100 mSv, with RAD23B showing the strongest correlation. Gene expression displayed high inter-individual variation with no dose-dependent changes or correlation with promoter methylation. Chronic LDIR exposure induces significant hypermethylation in specific DDR genes like RAD23B, DNMT3A, MRE11A, and BRCA1, suggesting a possible selective modulation of DNA repair pathways. but direct functional impact on gene expression was not observed in this study. The observed promoter methylation and gene expression alterations provide preliminary evidence of epigenetic modifications in response to chronic LDIR.