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γ 射线辐射后人外周血单个核细胞中碱基切除修复基因多态性(hOGG1、APE1、XRCC1 和 LIGASE1)与个体放射性敏感性及放射适应性反应的相关性

Radio-adaptive response, individual radio-sensitivity and correlation of base excision repair gene polymorphism (hOGG1, APE1, XRCC1, and LIGASE1) in human peripheral blood mononuclear cells exposed to gamma radiation.

机构信息

Low Level Radiation Research Section, Radiation Biology & Health Sciences Division, Bio-Sciences Group, Bhabha Atomic Research Centre, Trombay, Mumbai, India.

出版信息

Environ Mol Mutagen. 2020 Jun;61(5):551-559. doi: 10.1002/em.22383. Epub 2020 May 12.

Abstract

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.

摘要

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。

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