title: Albumin adducts of benzene oxide and 1,4-benzoquinone as measures of human benzene metabolism.
abstract: Albumin adducts of benzene oxide (BO-Alb) and 1,4-benzoquinone (1,4-BQ-Alb) were investigated among 134 workers exposed to benzene and 51 unexposed controls in Tianjin, China. Concentrations of both adducts increased with benzene exposure [range = 0.07-46.6 parts/million (ppm); median = 3.55 ppm] and with urinary cotinine. Adduct levels were less than proportional to benzene exposure, suggesting saturable CYP 2E1 metabolism of benzene. Because the transition from linear to saturable metabolism began at approximately 1 ppm, the common assumption of linear kinetics at much higher benzene exposures could lead to substantial underestimation of leukemia risks. Adduct levels were generally lower in older workers, indicating that CYP 2E1 metabolism diminished with age, at approximately 2%/year of life. The ratio of 1,4-BQ-Alb:BO-Alb decreased with age and coexposure to toluene, and increased with alcohol consumption. This indicates that factors affecting CYP 2E1 metabolism exerted a greater role on production of 1,4-BQ than BO, presumably because of the second oxidation step from phenol to hydroquinone. The adduct ratio was also positively associated with urinary cotinine, suggesting that both benzene and hydroquinone from cigarette smoke affected adduct levels. Results of a limited time course study of 11 subjects indicated moderate chemical instability of 1,4-BQ-Alb (half life = 13.5 days compared with 21 days for normal Alb turnover), whereas no evidence of instability of BO-Alb was observed. This study illustrates that Alb adducts can be used to investigate the dispositions of reactive metabolites of procarcinogens in humans, provided that exposures are adequately characterized in the month preceding blood collection.
authors.affiliation: School of Public Health, University of North Carolina, Chapel Hill, North Carolina 27599-7400, USA. stephen_rappaport@unc.edu
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Rappaport
authors.forename: Suramya
authors.initials: S
authors.lastname: Waidyanatha
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Qu
authors.forename: Roy
authors.initials: R
authors.lastname: Shore
authors.forename: Ximei
authors.initials: X
authors.lastname: Jin
authors.forename: Beverly
authors.initials: B
authors.lastname: Cohen
authors.forename: Lung-Chi
authors.initials: LC
authors.lastname: Chen
authors.forename: Assieh A
authors.initials: AA
authors.lastname: Melikian
authors.forename: Guilan
authors.initials: G
authors.lastname: Li
authors.forename: Songnian
authors.initials: S
authors.lastname: Yin
authors.forename: Huifang
authors.initials: H
authors.lastname: Yan
authors.forename: Bohong
authors.initials: B
authors.lastname: Xu
authors.forename: Ruidong
authors.initials: R
authors.lastname: Mu
authors.forename: Yuying
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhang
authors.forename: Keqi
authors.initials: K
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000418:Albumins / Q000378:metabolism*; D001554:Benzene / Q000378:metabolism*; D016227:Benzoquinones / Q000378:metabolism*; D003510:Cyclohexanes / Q000378:metabolism; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D012907:Smoking / Q000378:metabolism
chemical_list: D000418:Albumins; D016227:Benzoquinones; D003510:Cyclohexanes; C004532:quinone; D001554:Benzene; C023372:benzene oxide