Interactions between Exposure to Environmental Polycyclic Aromatic Hydrocarbons and DNA Repair Gene Polymorphisms on Bulky DNA Adducts in Human Sperm
Interactions between Exposure to Environmental Polycyclic Aromatic Hydrocarbons and DNA Repair Gene Polymorphisms on Bulky DNA Adducts in Human Sperm
复制标题
暴露于环境多环芳烃与人类精子中大体积 DNA 加合物的 DNA 修复基因多态性之间的相互作用
DOI：
10.1371/journal.pone.0013145
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发表时间：
2010-10-05
期刊：
影响因子：
3.7
通讯作者：
Wang, Xinru
中科院分区：
文献类型：
--
作者：
Ji, Guixiang;Gu, Aihua;Wang, Xinru
背景：核苷酸切除修复（NER）和碱基切除修复（BER）是化学试剂（如多环芳烃）引起的大体积加合物修复的主要机制。预计NER或BER基因的多态性可能调节个体对多环芳烃暴露的易感性。在这里，我们评估了多环芳烃暴露和NER和BER通路的多态性，单独或联合，对人类精子中多环芳烃- dna （PAH-DNA）加合物的影响。方法/主要发现：采用流式细胞术免疫荧光法测定465例不育成人精子的多环芳烃- dna加合物。采用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）技术检测XPA、XPD、ERCC1、XPF和XRCC1基因的多态性。多环芳烃暴露检测为尿1-羟基芘（1-OHP）水平。在校正潜在混杂因素的多变量模型中，我们观察到xrcc15 ' putr -T/C、Arg194Trp、Arg399Gln多态性与精子加合物水平升高有关。此外，分层分析表明，XRCC1 Arg194Trp、Arg399Gln多态性对多环芳烃dna加合物的不良影响仅在多环芳烃高暴露组中检测到。结论/意义：这些发现首次提供了XRCC1多态性可能改变精子多环芳烃-DNA加合物水平的证据，并可能作为识别多环芳烃暴露导致DNA损伤易感性个体的有用生物标志物。
Background: Nucleotide excision repair (NER) and base excision repair (BER) are the primary mechanisms for repair of bulky adducts caused by chemical agents, such as PAHs. It is expected that polymorphisms in NER or BER genes may modulate individual susceptibility to PAHs exposure. Here, we evaluate the effects of PAHs exposure and polymorphisms in NER and BER pathway, alone or combined, on polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adducts in human sperm.Methodology/Principal Findings: Sperm PAH-DNA adducts were measured by immunofluorescent assay using flow cytometry in a sample of 465 infertile adults. Polymorphisms of XPA, XPD, ERCC1, XPF, and XRCC1 were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. The PAHs exposure was detected as urinary 1-hydroxypyrene (1-OHP) levels. In multivariate models adjusted for potential confounders, we observed that XRCC1 5'pUTR -T/C, Arg194Trp, Arg399Gln polymorphisms were associated with increased sperm adduct levels. Furthermore, the stratified analysis indicated that adverse effects of XRCC1 Arg194Trp, Arg399Gln polymorphisms on PAH-DNA adducts were detected only in the high PAHs exposure group.Conclusions/Significance: These findings provided the first evidence that polymorphisms of XRCC1 may modify sperm PAH-DNA adduct levels and may be useful biomarkers to identify individuals susceptible to DNA damage resulting from PAHs exposure.