Occupational exposure to polycyclic aromatic hydrocarbons in German industries:: Association between exogenous exposure and urinary metabolites and its modulation by enzyme polymorphisms
Occupational exposure to polycyclic aromatic hydrocarbons in German industries:: Association between exogenous exposure and urinary metabolites and its modulation by enzyme polymorphisms
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DOI：
10.1016/j.toxlet.2005.02.012
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发表时间：
2005-07-04
影响因子：
3.5
通讯作者：
Br端ning, T
中科院分区：
文献类型：
--
作者：
Rihs, HP;Pesch, B;Br端ning, T
在170名德国工人中进行了一项横断面研究，暴露于多环芳烃（PAH），以探讨CYP 1A 1，CYP 1A 2，CYP 1B 1，CYP 3A 4，EPHX 1，GSTM 1，GST 1和GST 1的11个多态性在职业暴露于PAH和尿PAH代谢物之间的关联的作用。用实时PCR对多态性进行基因分型。通过个人空气采样测量16种PAH的暴露。在转换后测定1-羟基芘（1-OHP）和1-、2 + 9-、3-和4-羟基菲（OHPhe）总和的尿液浓度。尿1-OHP和OHPhe分别与外源性芘（斯皮尔曼r=0.52，p < 0.0001）和菲（斯皮尔曼r=0.72，p < 0.0001）显著相关。应用ANCOVA研究代谢物水平的潜在预测因素。目前的吸烟和行业类型被证明是预测1-OHP，但不是OHPhe。CYP 1A 1 3801 TC携带者的OHPhe水平是3801 TT携带者的1.6倍（p = 0.03）。与相应的参考基因型（113 YY; 139 HH）相比，EPHX 1 113 HH与较高的代谢物水平相关，139 RR与较低的代谢物水平相关。与GSTP 1114 AA相比，V等位基因携带者具有高1.5倍的1-OHP（p = 0.03）和高2倍的OHPhe浓度（p = 0.001）。OHPhe也是职业性PAH暴露的合适生物标志物。与环境PAH暴露和多态性的影响的关联更为明显的OPHe。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
A cross-sectional study was conducted in 170 German workers exposed to polycyclic aromatic hydrocarbons (PAH) to investigate the role of 11 polymorphisms of CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, GSTM1, GST1, and GSTP1 in the association between occupational exposure to PAH and urinary PAH metabolites. Polymorphisms were genotyped with real-time PCR. Exposure to 16 PAH was measured by personal air sampling. Urinary concentrations of 1-hydroxypyrene (1-OHP) and the sum of 1-, 2 + 9-, 3-, and 4-hydroxyphenanthrenes (OHPhe) were determined post-shift. Urinary 1-OHP and OHPhe correlated significantly with exogenous pyrene (Spearman r=0.52, p < 0.0001) and phenanthrene (Spearman r=0.72, p < 0.0001), respectively. ANCOVA was applied to investigate potential predictors of the metabolite levels. Current smoking and type of industry turned out to be predictors of 1-OHP but not of OHPhe. CYP1A1 3801TC carriers showed 1.6-fold higher OHPhe levels than 3801TT carriers (p = 0.03). EPHX1 113HH was associated with higher and 139RR with lower metabolite levels when compared with the corresponding reference genotypes (113YY; 139HH). In comparison to GSTP1 114AA, carriers of the V allele had 1.5-fold higher 1-OHP (p = 0.03) and 2-fold higher OHPhe concentrations (p = 0.001). OHPhe turned out to be also a suitable biomarker of occupational PAH exposure. The association with ambient PAH exposure and the influence of polymorphisms was more pronounced for OHPhe. (c) 2005 Elsevier Ireland Ltd. All rights reserved.