Albumin adducts of electrophilic benzene metabolites in benzene-exposed and control workers.
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.
Lin
Yu-Sheng
YS
Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, North Carolina 27599-7431, USA.
Vermeulen
Roel
R
Tsai
Chin H
CH
Waidyanatha
Suramya
S
Lan
Qing
Q
Rothman
Nathaniel
N
Smith
Martyn T
MT
Zhang
Luoping
L
Shen
Min
M
Li
Guilan
G
Yin
Songnian
S
Kim
Sungkyoon
S
Rappaport
Stephen M
SM
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
D000395:Air Pollutants, Occupational; D000418:Albumins; D016227:Benzoquinones; D015415:Biomarkers; D003510:Cyclohexanes; C004532:quinone; D001554:Benzene; C025225:2-benzoquinone; C023372:benzene oxide