Biomarkers of benzene: Urinary metabolites in relation to individual genotype and personal exposure

Abstract

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 μg/g creatinine/ppm benzene) was significantly lower than that in subjects with the wild type of GSTT1 (59.84 ± 47.66 μg/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.