ABSTRACT Coke plant workers' exposure to polycyclic aromatic hydrocarbons (PAHs) is monitored with the use of different biomarkers. The variations in genes coding enzymes involved in the first and the second phase of detoxification process can influence PAHs metabolites' production. While 1-hydroxypyrene urinary excretion was extensively examined in relationship to different gene variants, 3-hydroxybenzo[a]pyrene (3-OHBaP) is thought to more closely represent the carcinogenic fraction of PAHs intake. The aim of this study was to examine the relationship between the concentration of 3-OHBaP in the urine of coke plant workers and chosen variants of CYP1A1 (rs1048943 and rs4646903), CYP1B1 (rs1056836), and GST (GSTM1 null and GSTT1 null) genes. Urine samples were analyzed using HPLC method for 3-OHBaP, while polymerase chain reaction (PCR) methods were used for variants detection. 141 men took part in the study. Both CYP1A1 single nucleotide polymorphisms (SNPs) were found to be in complete linkage disequilibrium (rs1048943 is observed only as coexisting with rs4646903). In general, individuals with CYP1A1 variants had the lower concentration of the biomarker in urine, and the rs1048943 SNP was identified as more strongly correlated with this change of biomarker excretion, yielding three times lower concentrations at sampling time for rs1048943 heterozygote than for wild type. CYP1B1 rs1056836 SNP showed weak but statistically significant correlation with the change of biomarker excretion. The biomarker levels were on average 1.8-fold higher for heterozygotes and variant homozygotes at CYP1B1 rs1056836 locus than for wild type. No correlation was found for GSTM1 and GSTT1 null genotypes, smoking status, and air concentrations of benzo[a]pyrene and particulate matter.

中文翻译：

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解毒基因变异与焦化厂工人尿液中3-羟基苯并[a]芘浓度的关系

摘要使用不同的生物标志物监测焦炭厂工人接触多环芳烃 (PAH) 的情况。参与解毒过程第一阶段和第二阶段的编码酶基因的变化会影响多环芳烃代谢物的产生。虽然 1-羟基芘尿排泄与不同基因变异的关系得到广泛研究，但 3-羟基苯并 [a] 芘 (3-OHBaP) 被认为更接近代表多环芳烃摄入的致癌部分。本研究的目的是检查焦炭厂工人尿液中 3-OHBaP 的浓度与选定的 CYP1A1（rs1048943 和 rs4646903）、CYP1B1（rs1056836）和 GST（GSTM1 无效和 GSTT1 无效）基因变体之间的关系. 使用 HPLC 方法分析尿液样本中的 3-OHBaP，而聚合酶链反应（PCR）方法用于变异检测。141 名男性参加了这项研究。发现两个 CYP1A1 单核苷酸多态性 (SNP) 处于完全连锁不平衡状态（rs1048943 仅与 rs4646903 共存）。一般来说，具有 CYP1A1 变异的个体在尿液中具有较低浓度的生物标志物，并且 rs1048943 SNP 被鉴定为与生物标志物排泄的这种变化更密切相关，rs1048943 杂合子在采样时产生的浓度比野生型低三倍。CYP1B1 rs1056836 SNP与生物标志物排泄的变化显示出微弱但统计学上显着的相关性。CYP1B1 rs1056836 基因座的杂合子和变异纯合子的生物标志物水平平均比野生型高 1.8 倍。