Effect of DNA repair gene polymorphisms on BPDE-DNA adducts in human lymphocytes
Effect of DNA repair gene polymorphisms on BPDE-DNA adducts in human lymphocytes
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DOI：
10.1002/ijc.10463
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发表时间：
2002-07-01
影响因子：
6.4
通讯作者：
Airoldi, L
中科院分区：
文献类型：
--
作者：
Pastorelli, R;Cerri, A;Airoldi, L
为了确定DNA修复基因的变异是否与宿主DNA损伤有关，我们研究了一组男性肺癌患者（均为吸烟者）中XPD基因（密码子199，312，75 - 1）和XRCCI基因（密码子194，399）多态性与淋巴细胞DNA苯并（a）芘二羟环氧加合物（BPDE-DNA）的存在之间的关联。采用高分辨气相色谱-负离子化学电离-质谱联用技术对BPDE-DNA加合物进行分析。采用PCR-RFLP方法鉴定XPD和XRCCI基因型。XRCCI和XPD基因型不影响可检测的BPDE-DNA加合物的水平和比例。考虑到GSTMI在BPDE解毒中的作用，还对患者进行了GSTMI多态性基因分型。当GSTMI缺失的个体为XPD-Asp 312 Asp + Lys 751 Lys时，其BPDE-DNA加合物的水平显著高于至少一个变异等位基因的携带者。与XRCCI基因型没有发现这种关联。由于研究人群较小（n = 60），可能的基因-基因和基因-环境的进一步统计分析将不会提供信息。这是第一次在体内分析特异性BPDE-DNA加合物的多态性修复基因（XPD，XRCCI）和外源性代谢基因（GSTMI）。我们的研究结果提高了XPD-Asp 312 Asp + Lys 751 Lys基因型可能增加BPDE-DNA损伤的可能性;这种效应可能在特别可能累积损伤的个体中很明显，可能是因为较低的解毒能力和高环境暴露。(C)2002 Wiley-Liss，Inc.
To determine whether variations in DNA repair genes are related to host DNA damage, we investigated the association between polymorphism in the XPD gene (codon 199, 312, 75 1) and the XRCCI gene (codon 194, 399) and the presence of benzo(a)pyrene diolepoxide adducts to lymphocyte DNA (BPDE-DNA) in a group of male patients with incident lung cancer, all current smokers. BPDE-DNA adducts were analyzed by high-resolution gas chromatography-negative ion chemical ionization-mass spectrometry. XPD and XRCCI genotypes were identified by PCR-RFLP. XRCCI and XPD genotypes did not affect the levels and proportion of detectable BPDE-DNA adducts. The patients were also genotyped for the GSTMI polymorphism, given its role in the detoxification of BPDE. Individuals with the GSTMI deletion had significantly higher levels of BPDE-DNA adducts when they were XPD-Asp312Asp+Lys751Lys than carriers of at least one variant allele. No such association was found with the XRCCI genotypes. Because of the small study population (n = 60), further statistical analysis of possible gene-gene and gene-environment would not be informative. This is the first study analysing the specific BPDE-DNA adduct in vivo with regard to polymorphic repair genes (XPD, XRCCI) and xenobiotic metabolizing gene (GSTMI). Our results raise the possibility that the XPD-Asp312Asp+Lys751Lys genotype may increase BPDE-DNA damage; this effect might be evident in individuals who are especially likely to have accumulated damage, probably because of lower detoxification capacity and high environmental exposure. (C) 2002 Wiley-Liss, Inc.