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[ERCC2/XPD单核苷酸多态性与苯并[a]芘体外诱导的DNA加合物损伤之间的关联研究]

[Study on association between ERCC2/XPD single nucleotide polymorphisms and DNA adducts damage induced by B[a]P in vitro].

作者信息

Liu Yanhua, Yu Tao, Xiao Sha, Guan Yangyang, Li Dandan, Jin Cuihong, Liu Qiufang, Yang Jinghua, Wu Shengwen, Lu Xiaobo

机构信息

China Medical University, Public Health Institute, Toxicology Department, Shenyang 110001, China.

出版信息

Wei Sheng Yan Jiu. 2013 Jan;42(1):49-54.

Abstract

OBJECTIVE

To evaluate the association between DNA damage repair capacity induced by environment carcinogen benzo[a] pyrene (B [a] P) and ERCC2/XPD single nucleotide polymorphisms(SNP).

METHODS

8 ml peripheral bloods of 282 healthy ethnic Han people from Liao-ning province were collected, isolated lymphocytes and extracted DNA. The genotypes of ERCC2/XPD Lys751 Gln (rs13181), Asp312Asn (rs1799793), Arg156Arg (rs238406) were detected by Taqman real time PCR; BPDE-DNA adduct in vitro induced by B[a]P and S9 mixture in lymphocyte were detected by high performance liquid chromatography (HPLC).

RESULTS

The BPDE-DNA adduct levels of ERCC2/XPD Arg156Arg AA genotype were significantly higher than CC genotype. Compared with < or = 30 years, people at age of 50 - 70 years and > or = 70 years have higher BPDE-DNA adduct level (P < 0.05). Multiple covariates analysis showed SNP of ERCC2/XPD Arg156Arg (rs238406) and age have been related to BPDE-DNA adduct levels closely among all covariates (P < 0.05).

CONCLUSION

ERCC2/XPD Arg156Arg rs238406 polymorphisms may be associated with DNA repair capacity in excising BPDE-DNA adduct and A allele may increase the risks of cancer susceptibility.

摘要

目的

评估环境致癌物苯并[a]芘(B[a]P)诱导的DNA损伤修复能力与ERCC2/XPD单核苷酸多态性(SNP)之间的关联。

方法

采集282名辽宁汉族健康人群的8 ml外周血,分离淋巴细胞并提取DNA。采用Taqman实时荧光定量PCR检测ERCC2/XPD Lys751 Gln(rs13181)、Asp312Asn(rs1799793)、Arg156Arg(rs238406)的基因型;采用高效液相色谱法(HPLC)检测淋巴细胞中B[a]P和S9混合物体外诱导的BPDE-DNA加合物。

结果

ERCC2/XPD Arg156Arg AA基因型的BPDE-DNA加合物水平显著高于CC基因型。与≤30岁相比,50 - 70岁及≥70岁人群的BPDE-DNA加合物水平更高(P < 0.05)。多因素协变量分析显示,在所有协变量中,ERCC2/XPD Arg156Arg(rs238406)的SNP和年龄与BPDE-DNA加合物水平密切相关(P < 0.05)。

结论

ERCC2/XPD Arg156Arg rs238406多态性可能与切除BPDE-DNA加合物的DNA修复能力有关,A等位基因可能增加癌症易感性风险。

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