title: Albumin adducts of electrophilic benzene metabolites in benzene-exposed and control workers.
abstract: BACKGROUND
  Metabolism of benzene produces reactive electrophiles, including benzene oxide (BO), 1,4-benzoquinone (1,4-BQ), and 1,2-benzoquinone (1,2-BQ), that are capable of reacting with blood proteins to produce adducts.
  
  
  OBJECTIVE
  The main purpose of this study was to characterize relationships between levels of albumin adducts of these electrophiles in blood and the corresponding benzene exposures in benzene-exposed and control workers, after adjusting for important covariates. Because second blood samples were obtained from a subset of exposed workers, we also desired to estimate within-person and between-person variance components for the three adducts.
  
  
  METHODS
  We measured albumin adducts and benzene exposures in 250 benzene-exposed workers (exposure range, 0.26-54.5 ppm) and 140 control workers (exposure range < 0.01-0.53 ppm) from Tianjin, China. Separate multiple linear regression models were fitted to the logged adduct levels for workers exposed to benzene < 1 ppm and > or =1 ppm. Mixed-effects models were used to estimate within-person and between-person variance components of adduct levels.
  
  
  RESULTS
  We observed nonlinear (hockey-stick shaped) exposure-adduct relationships in log-scale, with inflection points between about 0.5 and 5 ppm. These inflection points represent air concentrations at which benzene contributed marginally to background adducts derived from smoking and from dietary and endogenous sources. Adduct levels were significantly affected by the blood-collection medium (serum or plasma containing either heparin or EDTA), smoking, age, and body mass index. When model predictions of adduct levels were plotted versus benzene exposure > or =1 ppm, we observed marked downward concavity, particularly for adducts of the benzoquinones. The between-person variance component of adduct levels increased in the order 1,2-BQ < 1,4-BQ < BO, whereas the within-person variance components of the three adducts followed the reverse order.
  
  
  CONCLUSIONS
  Although albumin adducts of BO and the benzoquinones reflect exposures to benzene > or = 1 ppm, they would not be useful biomarkers of exposure at ambient levels of benzene, which tend to be < 0.01 ppm, or in those working populations where exposures are consistently < 1 ppm. The concavity of exposure-adduct relationships is consistent with saturable metabolism of benzene at air concentrations > 1 ppm. The surprisingly large effect of the blood-collection medium on adduct levels, particularly those of the benzoquinones, should be further investigated.
authors: Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, North Carolina 27599-7431, USA.
authors: Yu-Sheng
authors: YS
authors: Lin
authors: Roel
authors: R
authors: Vermeulen
authors: Chin H
authors: CH
authors: Tsai
authors: Suramya
authors: S
authors: Waidyanatha
authors: Qing
authors: Q
authors: Lan
authors: Nathaniel
authors: N
authors: Rothman
authors: Martyn T
authors: MT
authors: Smith
authors: Luoping
authors: L
authors: Zhang
authors: Min
authors: M
authors: Shen
authors: Guilan
authors: G
authors: Li
authors: Songnian
authors: S
authors: Yin
authors: Sungkyoon
authors: S
authors: Kim
authors: Stephen M
authors: SM
authors: Rappaport
mesh_terms: D000293:Adolescent; D000328:Adult; D000395:Air Pollutants, Occupational / Q000378:metabolism*; D000418:Albumins / Q000378:metabolism*; D001554:Benzene / Q000378:metabolism*; D016227:Benzoquinones / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D002681:China; D003510:Cyclohexanes / Q000378:metabolism*; D004784:Environmental Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000032:analysis; D011485:Protein Binding; D012775:Shoes
chemical_list: D000395:Air Pollutants, Occupational; D000418:Albumins; D016227:Benzoquinones; D015415:Biomarkers; D003510:Cyclohexanes; C004532:quinone; D001554:Benzene; C025225:2-benzoquinone; C023372:benzene oxide