DNA methylation profile of repetitive element, DNA damage response and repair genes in human blood cells from normal and high level natural radiation areas of Kerala Coast, India

Biological effect of chronic low dose ionizing radiation was evaluated at molecular level on human population residing in normal and high level natural radiation areas (N and HLNRA) of Kerala coast. The level of radiation dose in Kerala coast varies from <1.0 mGy to 45 mGy/year. Studies conducted in this population showed reduction of DNA damage, efficient repair and active role of DNA damage response (DDR), DNA repair, Methylation and immune response genes in HLNRA. The objective of the present study is to find out the effect of chronic low dose radiation on DNA methylation profile of DDR, repair and repetitive element in blood cells of individuals from N and HLNRA population. Blood sample were collected from 42 healthy individuals from NLNRA (N=15), HLNRA Group I (1.51 -10.0 mGy/year, N= 18) and HLNRA Group II (>10.0 mGy/year, N=9). Genomic DNA isolated from peripheral blood mononuclear cells (PBMCs) was bisulphite converted and DNA methylation status was determined for repetitive element (LINE1) and promotor methylation status of ATM, RAD23B, MLH1, MGMT APC, DNMT3A, MRE11A, XPC, BRCA1, PARP1, MTHFR using Methyl sensitive high melting (MS-HRM) method. Gene expression of selected DDR and repair genes are also evaluated. LINE1, MTHFR and TNFα showed maximum % of methylation at basal level in NLNRA and HLNRA. BRCA1 and RAD23B genes showed hyper-methylation among HLNRA group II. ATM, APC and PARP1 showed similar pattern among NLNRA and HLNRA individuals. MLH1, XPC and MGMT remained un-methylated. Gene expression profile did not show significant changes at majority of the genes studied in HLNRA. Increased Promotor methylation observed at some of the DNA repair genes i.e., BRCA1 and RAD23B could be indicative of epigenetic signatures due to chronic low dose radiation. However, further studies with larger sample size are required to draw firm conclusion. (author)