Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark.
Free Radic Biol Med. 2012 Jan 1;52(1):118-25. doi: 10.1016/j.freeradbiomed.2011.09.038. Epub 2011 Oct 7.
Oxidatively damaged DNA base lesions are considered to be mainly repaired by 8-oxoguanine DNA glycosylase (OGG1) mediated pathways. We investigated the effect of the OGG1 Ser326Cys polymorphism on the level and repair of oxidatively damaged DNA in mononuclear blood cells (MNBC) by means of the comet assay. We collected blood samples from 1,019 healthy subjects and genotyped for the OGG1 Ser326Cys polymorphism. We found 49 subjects homozygous for the variant genotype (Cys/Cys) and selected same numbers of age-matched subjects with the heterozygous (Ser/Cys) and homozygous wild-type genotype (Ser/Ser). Carriers of the Cys/Cys genotype had higher levels of formamidopyrimidine DNA glycosylase (FPG) sensitive sites in MNBC (0.31 ± 0.03 lesions/10(6)bp) compared to Ser/Ser (0.19 ± 0.02 lesions/10(6)bp, P<0.01). The level of hOGG1 sensitive sites in MNBC from the Ser326Cys carriers (0.19 ± 0.16 lesions/10(6) bp) was also higher compared to the Ser/Ser genotype (0.11 ± 0.09 lesions/10(6) bp, P<0.05). Still, there was no genotype-related difference in DNA repair incision activity of MNBC extracts on nucleoids with oxidatively damaged DNA induced by Ro19-8022/white light (P=0.20). In addition, there were no differences in the expression of OGG1 (P=0.69), ERCC1 (P=0.62), MUTYH (P=0.85), NEIL1 (P=0.17) or NUDT1 (P=0.48) in whole blood. Our results indicate that the OGG1 Ser326Cys polymorphism has limited influence on the DNA repair incisions by extracts of MNBC, whereas the apparent increased risk of cancer in subjects with the Cys/Cys genotype may be because of higher levels of oxidatively damaged DNA.
氧化性损伤的 DNA 碱基损伤被认为主要通过 8-氧鸟嘌呤 DNA 糖基化酶（OGG1）介导的途径修复。我们通过彗星试验研究了 OGG1 Ser326Cys 多态性对单核细胞（MNBC）中氧化损伤 DNA 的水平和修复的影响。我们从 1019 名健康受试者中采集血液样本，并对 OGG1 Ser326Cys 多态性进行基因分型。我们发现 49 名受试者为变异基因型（Cys/Cys）纯合子，并选择相同数量年龄匹配的杂合子（Ser/Cys）和纯合野生型基因型（Ser/Ser）受试者。Cys/Cys 基因型携带者的 MNBC 中 formamidopyrimidine DNA 糖基化酶（FPG）敏感位点水平较高（0.31±0.03 个损伤/10^6bp），而 Ser/Ser 基因型（0.19±0.02 个损伤/10^6bp，P<0.01）。MNBC 中 Ser326Cys 携带者的 hOGG1 敏感位点水平（0.19±0.16 个损伤/10^6bp）也高于 Ser/Ser 基因型（0.11±0.09 个损伤/10^6bp，P<0.05）。然而，MNBC 提取物在 Ro19-8022/白光诱导的氧化损伤 DNA 核小体上的 DNA 修复切口活性与基因型无关（P=0.20）。此外，全血中 OGG1（P=0.69）、ERCC1（P=0.62）、MUTYH（P=0.85）、NEIL1（P=0.17）或 NUDT1（P=0.48）的表达也没有差异。我们的结果表明，OGG1 Ser326Cys 多态性对 MNBC 提取物的 DNA 修复切口影响有限，而具有 Cys/Cys 基因型的受试者癌症风险增加可能是由于氧化损伤 DNA 水平较高。
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