Low Level Radiation Research Section, Radiation Biology & Health Sciences Division, Bio-Sciences Group, Bhabha Atomic Research Centre, Trombay, Mumbai, India.
Environ Mol Mutagen. 2020 Jun;61(5):551-559. doi: 10.1002/em.22383. Epub 2020 May 12.
Radio-adaptive response (RAR) is a biological mechanism, where cells primed with a low dose exhibit reduced DNA damage with a high challenging dose. Single nucleotide polymorphisms (SNPs) of DNA repair genes including base excision repair (BER) pathway are known to be associated with radio-sensitivity but involvement in RAR is not yet understood. In the present study, attempt was made to correlate genotype frequencies of four BER SNPs [hOGG1(Ser326Cys), XRCC1(Arg399Gln), APE1(Asp148Glu) and LIGASE1(A/C)] with DNA damage, repair and mRNA expression level among 20 healthy donors (12 adaptive and 8 nonadaptive). Our results revealed that LIGASE1 (p = .002) showed significant correlation with DNA damage and mRNA expression level with increasing dose. hOGG1 (Ser326Cys), XRCC1 (Arg399Gln) and LIGASE1(A/C) polymorphisms showed significant difference with DNA damage (%T) and mRNA expression profile in primed cells among adaptive donors. In conclusion, BER gene polymorphisms play important role in identifying donors with radio-sensitivity and RAR in human cells.
放射适应反应(RAR)是一种生物学机制,其中细胞用低剂量预先处理后,用高挑战性剂量照射时会显示出减少的 DNA 损伤。已知 DNA 修复基因(包括碱基切除修复(BER)途径)的单核苷酸多态性(SNP)与放射敏感性有关,但在 RAR 中的作用尚不清楚。在本研究中,我们试图将四个 BER SNPs [hOGG1(Ser326Cys)、XRCC1(Arg399Gln)、APE1(Asp148Glu)和 LIGASE1(A/C)]的基因型频率与 20 名健康供体(12 名适应性和 8 名非适应性)之间的 DNA 损伤、修复和 mRNA 表达水平相关联。我们的结果表明,LIGASE1(p =.002)与 DNA 损伤和随剂量增加的 mRNA 表达水平呈显著相关。hOGG1(Ser326Cys)、XRCC1(Arg399Gln)和 LIGASE1(A/C)多态性在适应性供体的预刺激细胞中与 DNA 损伤(%T)和 mRNA 表达谱显示出显著差异。总之,BER 基因多态性在鉴定人类细胞中的放射敏感性和 RAR 供体方面起着重要作用。