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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.
Environmental and Molecular Mutagenesis ( IF 2.8 ) Pub Date : 2020-04-23 , DOI: 10.1002/em.22383
Sneh M Toprani 1 , Birajalaxmi Das 1
Affiliation  

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.

中文翻译:

暴露于伽马射线的人外周血单核细胞中的放射适应性反应,个体放射敏感性和碱基切除修复基因多态性(hOGG1,APE1,XRCC1和LIGASE1)的相关性。

放射自适应反应(RAR)是一种生物学机制,低剂量引发的细胞在高挑战剂量下显示出降低的DNA损伤。已知DNA修复基因的单核苷酸多态性(SNP)包括碱基切除修复(BER)途径与放射敏感性有关,但目前尚不了解其参与RAR。在本研究中,我们尝试将20种BER SNP [ hOGG1(Ser326Cys),XRCC1(Arg399Gln),APE1(Asp148Glu)和LIGASE1(A / C)]的基因型频率与DNA损伤,修复和mRNA表达水平相关联。健康的供体(12个适应性和8个非适应性)。我们的结果表明,LIGASE1p= .002)显示剂量增加与DNA损伤和mRNA表达水平显着相关。hOGG1Ser326Cys),XRCC1(Arg399Gln)和LIGASE1(A / C)多态性与适应性供体之间的致敏细胞中DNA损伤(%T)和mRNA表达谱具有显着差异。总之,BER基因多态性在鉴定人类细胞中具有放射敏感性和RAR的供体中起着重要作用。
更新日期:2020-04-23
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