The influence of cytochrome P450 1A1 and glutathione S-transferase M1 genotypes on biomarker levels in coke-oven workers
The influence of cytochrome P450 1A1 and glutathione S-transferase M1 genotypes on biomarker levels in coke-oven workers
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DOI：
10.1007/s002040050632
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发表时间：
1999-11-01
影响因子：
6.1
通讯作者：
Assennato, G
中科院分区：
文献类型：
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作者：
Brescia, G;Celotti, L;Assennato, G
本研究旨在评估基因-环境相互作用对多环芳烃暴露的焦炉工人不同生物标志物水平的影响。为了评估一些生物标志物（PAH-DNA加合物、硝基pah加合物到Hb和MN频率）的水平是否可以通过CYP1A1和GSTM1的遗传代谢多态性来调节，我们通过PCR分析了76名焦炉工人和18名对照者的CYP1A1 （MspI和Ile/Val位点）和GSTM1基因型。我们通过分层分析和逻辑回归模型分析了特定生物标志物与多环芳烃总暴露（尿中l-羟基芘水平）的相关性。在高暴露组（即高水平的1-OHP）中检测到高水平的PAH-DNA加合物的GSTM1-易感者比GSTM1+易感者和CYP1A1 Ile/Val易感者比CYP1A1 Ile/Ile易感者的比例更高，具有统计学意义（P = 0.03和P = 0.01）。在logistic回归模型中，PAH- dna加合物水平升高与GSTM1-基因型易感之间存在统计学意义上的相关性（P.O.R. = 4.18, P = 0.03）， PAH暴露与GSTM1-基因型对PAH- dna加合物有显著的交互作用。没有观察到这些代谢基因型对MN频率和硝基多环芳烃加合物对Hb的影响。总之，多环芳烃暴露与参与多环芳烃激活（CYP1A1）和解毒（GSTM1）的两种代谢基因型之间存在基因-环境相互作用。
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 l-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.