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Title: Protein adducts as biomarkers of human benzene metabolism.

Authors: Rappaport, Stephen M; Waidyanatha, Suramya; Yeowell-O'Connell, Karen; Rothman, Nathaniel; Smith, Martyn T; Zhang, Luoping; Qu, Qingshan; Shore, Roy; Li, Guilan; Yin, Songnian

Published In Chem Biol Interact, (2005 May 30)

Abstract: We used cysteinyl adducts of serum albumin (Alb) to investigate the production of two reactive benzene metabolites, namely, benzene oxide (BO) and 1,4-benzoquinone (1,4-BQ) in workers exposed to benzene. Adducts were measured in 160 benzene-exposed workers who did not use respiratory protection (based upon individual geometric mean benzene exposure levels: median=5.27 ppm, interquartile range=2.14-13.4 ppm, range=0.074-328 ppm) and 101 local controls, from populations in Shanghai and Tianjin, China. After isolation of Alb, these adducts (designated as BO-Alb and 1,4-BQ-Alb) were cleaved from the protein with methanesulfonic acid and trifluoroacetic anhydride and measured by gas chromatography-mass spectrometry. Although BO-Alb and 1,4-BQ-Alb were measured in all subjects, levels of both adducts were 2.4-fold greater (median value) in exposed subjects than in controls (interquartile-fold range=1.63-4.05 for BO-Alb and 1.64-3.69 for 1,4-BQ-Alb). Log-log plots of the individual adduct levels versus exposure were quasi-linear with straight-line slopes of about 0.3 for both BO-Alb and 1,4-BQ-Alb. Since these log-space slopes were significantly less than one, we infer that adduct production was nonlinear, i.e., less-than proportional to benzene exposure, over the indicated range. This behavior points to saturation of CYP2E1 as a critical metabolic consequence of high exposure to benzene in humans. Thus, the biologically effective dose of BO and 1,4-BQ should be proportionally greater in persons exposed to low rather than high levels of benzene.

PubMed ID: 15935805 Exiting the NIEHS site

MeSH Terms: Benzene/analysis; Benzene/metabolism*; Benzoquinones/metabolism*; Biomarkers; China/epidemiology; Cyclohexanes/metabolism*; Dose-Response Relationship, Drug; Environmental Monitoring; Epidemiological Monitoring; Female; Humans; Male; Occupational Exposure*; Protein Binding; Serum Albumin/metabolism*

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