Qu Qingshan, Shore Roy, Li Guilan, Su Lin, Jin Ximei, Melikian Asseih A, Roy Nirmal, Chen Lung Chi, Wirgin Isaac, Cohen Beverly, Yin Songnian, Li Yuying, Mu Ruidong
Nelson Institute of Environmental Medicine, New York University School of Medicine, USA.
Chem Biol Interact. 2005 May 30;153-154:85-95. doi: 10.1016/j.cbi.2005.03.012. Epub 2005 Apr 8.
This report is part of an extensive biomarker study conducted in a Chinese occupational population with benzene exposures ranging from 0.06 to 122 ppm (median exposure of 3.2 ppm). All urinary benzene metabolites measured in this study were significantly elevated after exposure to benzene at or above 5 ppm. Among these metabolites, however, only S-phenylmercapturic acid (S-PMA) and trans,trans-muconic acid (t,t-MA) showed a significant exposure-response trend over the exposure range from 0 to 1 ppm (for S-PMA, p<0.0001 and for t,t-MA, p=0.006). For benzene exposure monitoring, both S-PMA and t,t-MA were judged to be good and sensitive markers, which detected benzene exposure at around 0.1 and 1 ppm, respectively. Polymorphisms of the metabolic genes, including CYP2E1, quinone oxidoreductase (NQO1), GSTT1, and myeloperoxidase (MPO), were identified and did not show significant effects on the formation of metabolites, except GSTT1 on S-PMA. The production rate of S-PMA from benzene in exposed workers with GSTT1 null alleles (24.72+/-32.48 microg/g creatinine/ppm benzene) was significantly lower than that in subjects with the wild type of GSTT1 (59.84+/-47.66 microg/g creatinine/ppm benzene, p<0.0001). Further regression analysis of S-PMA production rate on GSTT1 genotype with adjustment of sex, age, benzene exposure, and cotinine levels indicated that the genotype of GSTT1 plays a critical role in determining the inter-individual variations of S-PMA formation from benzene exposure. Therefore, the individual genotype of GSTT1 needs to be identified and considered while using S-PMA as a marker to estimate the personal exposure levels of benzene in future population studies.
本报告是一项针对中国职业人群开展的广泛生物标志物研究的一部分，该人群的苯暴露水平在0.06至122 ppm之间（中位暴露水平为3.2 ppm）。本研究中测量的所有尿苯代谢物在苯暴露水平达到或高于5 ppm后均显著升高。然而，在这些代谢物中，只有S-苯基巯基尿酸（S-PMA）和反式，反式-粘康酸（t,t-MA）在0至1 ppm的暴露范围内呈现出显著的暴露-反应趋势（对于S-PMA，p<0.0001；对于t,t-MA，p=0.006）。对于苯暴露监测，S-PMA和t,t-MA均被判定为良好且敏感的标志物，它们分别在约0.1 ppm和1 ppm时检测到苯暴露。对包括细胞色素P450 2E1（CYP2E1）、醌氧化还原酶（NQO1）、谷胱甘肽S-转移酶T1（GSTT1）和髓过氧化物酶（MPO）在内的代谢基因多态性进行了鉴定，结果显示除GSTT1对S-PMA有影响外，其他基因多态性对代谢物的形成均无显著影响。GSTT1基因缺失等位基因的暴露工人中，苯生成S-PMA的速率（24.72±32.48微克/克肌酐/ppm苯）显著低于具有GSTT1野生型的受试者（59.84±47.66微克/克肌酐/ppm苯，p<0.0001）。对GSTT1基因型进行S-PMA生成速率的进一步回归分析，并对性别、年龄、苯暴露和可替宁水平进行校正，结果表明GSTT1基因型在决定苯暴露后S-PMA形成的个体间差异方面起着关键作用。因此，在未来人群研究中使用S-PMA作为标志物来估计个人苯暴露水平时，需要鉴定并考虑个体的GSTT1基因型。
