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首页> 外文期刊>Archives of Toxicology >The influence of cytochrome P450 1A1 and glutathione S-transferase M1 genotypes on biomarker levels in coke-oven workers.
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The influence of cytochrome P450 1A1 and glutathione S-transferase M1 genotypes on biomarker levels in coke-oven workers.

机译：细胞色素P450 1A1和谷胱甘肽S-转移酶M1基因型对焦炉工人生物标志物水平的影响。

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The present study has the aim of evaluating gene-environment interaction on the levels of different biomarkers in coke-oven workers exposed to PAH. In order to assess whether the levels of some biomarkers (PAH-DNA adducts, nitro-PAH adducts to Hb and MN frequency) could be modulated by the genetic metabolic polymorphisms for CYP1A1 and GSTM1, we analysed in 76 coke-oven workers and 18 controls the CYP1A1 (MspI and Ile/Val sites) and the GSTM1 genotypes by a PCR assay. In individuals with shared setup of CYP1A1 or GSTM1 genotypes, we analysed how the specified biomarkers correlated with total PAH exposure (urinary levels of 1-hydroxypyrene) both by a stratified analysis and logistic regression modelling. Statistically significant (P = 0.03 and P = 0.01) higher percentages of the more susceptible GSTM1- subjects compared to the GSTM1+ subjects and of the more susceptible CYP1A1 Ile/Val individuals compared to the CYP1A1 Ile/Ile individuals were detected for high levels of PAH-DNA adducts in the high exposure group (namely high levels of 1-OHP). A statistically significant association was observed between increased PAH-DNA adduct levels and the more susceptible GSTM1- genotype (P.O.R. = 4.18, P = 0.03) in a logistic regression modelling and a significant interaction between PAH exposure and GSTM1-genotype was found for PAH-DNA adducts. No effect of these metabolic genotypes was observed for MN frequency and nitro-PAH adducts to Hb. In conclusion, a gene-environment interaction between PAH exposure and two metabolic genotypes involved in activation (CYP1A1) and detoxification (GSTM1) of PAHs, respectively, has been identified.
机译：本研究旨在评估暴露于PAH的焦炉工人中不同生物标记物水平上的基因-环境相互作用。为了评估CYP1A1和GSTM1的遗传代谢多态性是否可以通过CYP1A1和GSTM1的遗传代谢多态性来调节某些生物标志物的水平（PAH-DNA加合物，Hb和MN频率的硝基PAH加合物），我们分析了76位焦炉工人和18位对照CYP1A1（MspI和Ile / Val位点）和GSTM1基因型通过PCR测定。在具有CYP1A1或GSTM1基因型共享设置的个体中，我们通过分层分析和逻辑回归模型分析了特定的生物标记物与总PAH暴露（尿液中的1-羟基py）的相关性。检测到较高的PAH水平具有统计学显着性（P = 0.03和P = 0.01），与GSTM1 +受试者相比，更易感的GSTM1受试者和与CYP1A1 Ile / Ile受试者相比，较易感的CYP1A1 Ile / Val受试者的百分比更高-高暴露组（即高水平的1-OHP）中的DNA加合物。在Logistic回归模型中观察到PAH-DNA加合物水平增加与更易感的GSTM1-基因型（POR = 4.18，P = 0.03）之间存在统计学上的显着关联，并且PAH-的PAH暴露与GSTM1-基因型之间存在显着的相互作用。 DNA加合物。对于MN频率和Hb的硝基PAH加合物，未观察到这些代谢基因型的影响。总之，已经确定了PAH暴露与分别参与PAHs活化（CYP1A1）和解毒（GSTM1）的两种代谢基因型之间的基因-环境相互作用。

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