Benzo[a]pyrene(B[a]P), and its ultimate metabolite Benzo[a]pyrene 7,8-diol 9,10-epoxide (BPDE), are classic DNA damaging carcinogens. DNA damage in cells caused by BPDE is normally repaired by Nucleotide Excision Repair (NER) and Base Excision Repair (BER). Genetic variations in NER and BER can change individual DNA repair capacity to DNA damage induced by BPDE. In the present study we determined the number of in vitro induced BPDE-DNA adducts in lymphocytes, to reflect individual susceptibility to Polycyclic aromatic hydrocarbons (PAHs)-induced carcinogenesis. The BPDE-DNA adduct level in lymphocytes were assessed by high performance liquid chromatography (HPLC) in 281 randomly selected participants. We genotyped for 9 single nucleotide polymorphisms (SNPs) in genes involved in NER (XPB rs4150441, XPC rs2228001, rs2279017 and XPF rs4781560), BER (XRCC1 rs25487, rs25489 and rs1799782) and genes located on chromosome 19q13.2-3 (PPP1R13L rs1005165 and CAST rs967591). We found that 3 polymorphisms in chromosome 19q13.2-3 were associated with lower levels of BPDE-DNA adducts (MinorT allele in XRCC1 rs1799782, minor T allele in PPP1R13L rs1005165 and minor A allele in CAST rs967571). In addition, a modified comet assay was performed to further confirm the above conclusions. We found both minor T allele in PPP1R13L rs1005165 and minor A allele in CAST rs967571 were associated with the lower levels of BPDE-adducts. Our data suggested that the variant genotypes of genes in chromosome 19q13.2-3 are associated with the alteration of repair efficiency to DNA damage caused by Benzo[a]pyrene, and may contribute to enhance predictive value for individual's DNA repair capacity in response to environmental carcinogens.

中文翻译：

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与原代培养淋巴细胞中 BPDE-DNA 加合物修复能力改变相关的 19q13.3 基因的遗传多态性。

苯并[a]芘(B[a]P)及其最终代谢物苯并[a]芘7,8-二醇9,10-环氧化物(BPDE)是典型的DNA损伤致癌物。由 BPDE 引起的细胞 DNA 损伤通常由核苷酸切除修复 (NER) 和碱基切除修复 (BER) 修复。NER 和 BER 的遗传变异可以改变个体 DNA 对 BPDE 诱导的 DNA 损伤的修复能力。在本研究中，我们确定了淋巴细胞中体外诱导的 BPDE-DNA 加合物的数量，以反映个体对多环芳烃 (PAH) 诱导的致癌作用的易感性。通过高效液相色谱 (HPLC) 在 281 名随机选择的参与者中评估淋巴细胞中的 BPDE-DNA 加合物水平。我们对涉及 NER 的基因（XPB rs4150441、XPC rs2228001、rs2279017 和 XPF rs4781560）中的 9 个单核苷酸多态性 (SNP) 进行基因分型，BER（XRCC1 rs25487、rs25489 和 rs1799782）和位于染色体 19q13.2-3 上的基因（PPP1R13L rs1005165 和 CAST rs967591）。我们发现染色体 19q13.2-3 中的 3 个多态性与较低水平的 BPDE-DNA 加合物（XRCC1 rs1799782 中的 MinorT 等位基因、PPP1R13L rs1005165 中的次要 T 等位基因和 CAST rs967571 中的次要 A 等位基因）相关。此外，还进行了改良的彗星试验以进一步证实上述结论。我们发现 PPP1R13L rs1005165 中的次要 T 等位基因和 CAST rs967571 中的次要 A 等位基因都与较低水平的 BPDE 加合物相关。我们的数据表明，染色体 19q13.2-3 中基因的变异基因型与苯并[a]芘引起的 DNA 损伤修复效率的改变有关，可能有助于提高个体的预测价值。