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。
