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

Shridevi Shelke,Birajalaxmi Das

doi:10.1186/s41021-021-00176-4

Abstract

BackgroundRadio-adaptive response (RAR) is transient phenomena, where cells conditioned with a small dose (priming) of ionizing radiation shows significantly reduced DNA damage with a subsequent high challenging dose. The role of DNA double strand break repair gene polymorphism in RAR is not known. In the present study attempt was made to find out the influence of NHEJ repair gene polymorphisms [a VNTR; XRCC5 (3R/2R/1R/0R); two single nucleotide polymorphisms (SNPs); XRCC6 (C/G) and XRCC7 (G/T)] with DNA damage, repair and mRNA expression in human PBMCs in dose and adaptive response studies. Genomic DNA extracted from venous blood samples of 20 random healthy donors (16 adaptive and 4 non-adaptive) and genotyping of NHEJ repair genes was carried out using PCR amplified length polymorphism.ResultsThe dose response study revealed significant positive correlation of genotypes at XRRC5 (3R/2R/1R/0R), XRCC6(C/G) and XRCC7 (G/T) with DNA damage. Donors having genotypes with 2R allele at XRCC5 showed significant positive correlation with mRNA expression level (0R/2R: r = 0.846, P = 0.034; 1R/2R: r = 0.698, P = 0.0001 and 2R/2R: r = 0.831, P = 0.0001) for dose response. Genotypes C/C and C/G of XRCC6 showed a significant positive correlation (P = 0.0001), whereas, genotype T/T of XRCC7 showed significant negative correlation (r = − 0.376, P = 0.041) with mRNA expression.ConclusionInterestingly, adaptive donors having C/G genotype of XRCC6 showed significantly higher (P < 0.05) mRNA expression level in primed cells suggesting their role in RAR. In addition, NHEJ repair gene polymorphisms play crucial role with radio-sensitivity and RAR in human PBMCs.

Highlights

Environmental exposures such as chemical and physical mutagens including ionizing radiation may (IR) pose concern to human health
DNA polymorphism study of XRCC5 (KU80), XRCC6 (KU70) and XRCC7 (PRKDC) genes were carried out among 20 donors and the genotypes were correlated with the DNA damage, repair and transcriptional profile
Linear regression was carried out for dose response study at DNA damage and gene expression level at each of the genotypes to find out the association of polymorphisms at these above genes with DNA damage, mRNA expression and inter-individual variation if any

Summary

Introduction

Environmental exposures such as chemical and physical mutagens including ionizing radiation may (IR) pose concern to human health. Mis-repaired or defective cells accumulate lethal mutations, rearrangement of complex chromosomal aberrations or chromothripsis [2, 3] These changes activate DNA damage response (DDR), cell cycle check points, and cell survival pathways along with molecular pathways of DNA repair. Radio-adaptive response (RAR) occurs in cells/tissues, when an exposure of low dose (priming dose) of IR helps in reducing the damage caused by a single high dose (challenging dose) of IR [4]. Radio-adaptive response (RAR) is transient phenomena, where cells conditioned with a small dose (priming) of ionizing radiation shows significantly reduced DNA damage with a subsequent high challenging dose. Genomic DNA extracted from venous blood samples of 20 random healthy donors (16 adaptive and 4 non-adaptive) and genotyping of NHEJ repair genes was carried out using PCR amplified length polymorphism

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