Global transcriptome profile reveals abundance of DNA damage response and repair genes in individuals from high level natural radiation areas of Kerala coast

Abstract

The high level natural radiation areas (HLNRA) of Kerala coast in south west India is unique for its wide variation in the background radiation dose (<1.0mGy to 45mGy/year) and vast population size. Several biological studies conducted in this area did not reveal any adverse effects of chronic low dose and low dose rate radiation on human population. In the present study, global transcriptome analysis was carried out in peripheral blood mono-nuclear cells of 36 individuals belonging to different background dose groups [NLNRA, (Group I, ≤1.50 mGy/year) and three groups of HLNRA; Group II, 1.51–5.0 mGy/year), Group III, 5.01-15mGy/year and Group IV, >15.0 mGy/year] to find out differentially expressed genes and their biological significance in response to chronic low dose radiation exposure. Our results revealed a dose dependent increase in the number of differentially expressed genes with respect to different background dose levels. Gene ontology analysis revealed majority of these differentially expressed genes are involved in DNA damage response (DDR) signaling, DNA repair, cell cycle arrest, apoptosis, histone/chromatin modification and immune response. In the present study, 64 background dose responsive genes have been identified as possible chronic low dose radiation signatures. Validation of 30 differentially expressed genes was carried out using fluorescent based universal probe library. Abundance of DDR and DNA repair genes along with pathways such as MAPK, p53 and JNK in higher background dose groups (> 5.0mGy/year) indicated a possible threshold dose for DDR signaling and are plausible reason of observing in vivo radio-adaptive response and non-carcinogenesis in HLNRA population. To our knowledge, this is the first study on molecular effect of chronic low dose radiation exposure on human population from high background radiation areas at transcriptome level using high throughput approach. These findings have tremendous implications in understanding low dose radiation biology especially, the effect of low dose radiation exposure in humans.

Assessment of Adaptive Response of Gamma Radiation in the Operating Room Personnel Exposed to Anesthetic Gases by Measuring the Relative Gene Expression Changes Ku80, Ligase1 and P53

“…Similarly, in another study, P53 expression in radiation workers was significantly higher than that of the control group and showed that low and chronic doses of ionizing radiation play an important role in increasing the expression of P53 amongst radiation workers [21]. In several studies, the role of P53 in radio-adaptive response was reported [22][23][24]. Regarding the results of our research and previous studies, P53 expression is important for the safety of workers exposed to genotoxic agents such as ionizing radiation and anesthetic gases.…”

Radio-adaptive response and correlation of non-homologous end joining repair gene polymorphisms [XRRC5 (3R/2R/1R/0R), XRCC6(C/G) and XRCC7 (G/T)] in human peripheral blood mononuclear cells exposed to gamma radiation

“…DDR induced by genotoxic stress including IR lead to alteration of gene expression profile in human cells [ 17 , 18 ]. Several studies have demonstrated early and late responses of miRNA expression of several genes involved in various cellular and molecular processes in human cells in response to IR.…”

“…Both homologous recombination repair (HRR) or non-homologous end-joining (NHEJ) repair mechanisms are activated due to LDIR exposure in cell lines in culture, but NHEJ is more active in resting PBMCs. Recent studies from high level natural background radiation areas have shown efficient repair of DSBs and activation of DDR, NHEJ, HR and other signaling pathways in PBMCs at low lose radiation exposed human population [ 16 , 17 ]. Evidences of the involvement DDR and BER repair pathway in human PBMCs have also been found at DNA damage, repair and mRNA expression level [ 18 – 20 ].…”

Low dose ionizing radiation effects on the immune system

“…Despite the fact that the cited studies focused on different immune parameters their conclusions were quite convergent, showing increased activity in the adaptive immune response and the presence of pro-inflammatory factors. A recent study on gene expression profiles of PBMCs from inhabitants of the high level background radioactivity area in Kerala, India found that immune response pathways were among the radiation-affected over-represented pathways ( Jain and Das, 2017 ).…”