Correlation between base-excision repair gene polymorphisms and levels of in-vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes.
Correlation between base-excision repair gene polymorphisms and levels of in-vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes.
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DOI：
10.1371/journal.pone.0040131
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wei Q
中科院分区：
文献类型：
--
作者：
Yu H;Zhao H;Wang LE;Liu Z;Li D;Wei Q
体外培养的外周淋巴细胞中苯并[a]芘二醇环氧化物 (BPDE) 诱导的 DNA 加合物已被证明是与癌症风险相关的个体 DNA 修复表型的表型生物标志物。在这项研究中，我们探讨了碱基切除修复基因（PARP1 Val762Ala、APEX1 Asp148Glu 和 XRCC1 Arg399Gln）的基因型与体外培养的 706 名无癌非西班牙裔白人受试者外周血淋巴细胞中 BPDE 诱导的 DNA 加合物之间的关联。我们发现，曾经吸烟者中 BPDE 诱导的 DNA 加合物水平显着高于从不吸烟者，并且具有 Glu 变异基因型（即 Asp/Glu 和 Glu/Glu）的个体表现出比具有常见 Asp/Asp 纯合基因型的个体更低的 BPDE 诱导 DNA 加合物水平（中位 RAL 水平：Asp/Asp 为 32.0，Asp/Asp 为 27.0） Asp/Glu 和 Glu/Glu 分别为 17.0；P 趋势 = 0.030)。进一步分层分析显示，与常见 APEX1-148 纯合 Asp/Asp 基因型个体相比，APEX1-148Asp/Glu 基因型或 Glu/Glu 基因型个体产生较高水平加合物的风险较低（调整后 OR = 0.60，95% CI：0.36–0.98，调整后 OR = 0.60，95% CI：0.36–0.98）吸烟者中 OR = 0.47，95% CI：0.26–0.86；P 趋势 = 0.012）。在非吸烟者中没有观察到这种效果。然而，在本研究人群中，APEX1 Asp148Glu 多态性与吸烟暴露之间没有显着的相互作用（P = 0.512）。额外的基因型-表型分析发现，APEX1-148Glu 等位基因在 270 个 Epstein-Barr 病毒转化的淋巴母细胞系中显着增加了 APEX1 mRNA 的表达，这可能与更活跃的修复活性有关。我们的研究结果表明，功能性 APEX1-148Glu 等位基因与高水平 BPDE 诱导的高水平 mRNA 表达介导的 DNA 加合物的风险降低相关。
In vitro benzo[a]pyrene diol epoxide (BPDE)-induced DNA adducts in cultured peripheral lymphocytes have been shown to be a phenotypic biomarker of individual’s DNA repair phenotype that is associated with cancer risk. In this study, we explored associations between genotypes of base-excision repair genes (PARP1 Val762Ala, APEX1 Asp148Glu, and XRCC1 Arg399Gln) and in vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes in 706 cancer-free non-Hispanic white subjects. We found that levels of BPDE-induced DNA adducts were significantly higher in ever smokers than in never smokers and that individuals with the Glu variant genotypes (i.e., Asp/Glu and Glu/Glu) exhibited lower levels of BPDE-induced DNA adducts than did individuals with the common Asp/Asp homozygous genotype (median RAL levels: 32.0 for Asp/Asp, 27.0 for Asp/Glu, and 17.0 for Glu/Glu, respectively; P trend = 0.030). Further stratified analysis showed that compared with individuals with the common APEX1-148 homozygous Asp/Asp genotype, individuals with the APEX1-148Asp/Glu genotype or the Glu/Glu genotype had a lower risk of having higher-level adducts (adjusted OR = 0.60, 95% CI: 0.36–0.98 and adjusted OR = 0.47, 95% CI: 0.26–0.86, respectively; P trend = 0.012) among smokers. Such an effect was not observed in non-smokers. However, there was no significant interaction between the APEX1 Asp148Glu polymorphism and smoking exposure in this study population (P = 0.512). Additional genotype-phenotype analysis found that the APEX1-148Glu allele had significantly increased expression of APEX1 mRNA in 270 Epstein-Barr virus-transformed lymphoblastoid cell lines, which is likely associated with more active repair activity. Our findings suggest that the functional APEX1-148Glu allele is associated with reduced risk of having high levels of BPDE-induced DNA adducts mediated with high levels of mRNA expression.
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DOI：
10.1016/0921-8777(90)90030-9
发表时间：
1990-07-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
BLAKEY, DH;DOUGLAS, GR
通讯作者：
DOUGLAS, GR
影响因子：
3
作者：
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影响因子：
64.8
作者：
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Tanaka, T
影响因子：
4.7
作者：
Braithwaite, E;Wu, XH;Wang, ZG
通讯作者：
Wang, ZG
影响因子：
5.3
作者：
Hess, MT;Gunz, D;Naegeli, H
通讯作者：
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