Carcinogenesis, Vol. 21, No. 1, 55-62,
January 2000
© 2000 Oxford University Press
Molecular Epidemiology and Cancer Prevention |
Genotoxic markers among butadiene polymer workers in China
1 Occupational Studies Branch, National Cancer Institute, Bethesda, MD, USA,
2 School of Public Health, University of California, Berkeley, CA, USA,
3 Chinese Academy of Preventive Medicine, Beijing, China,
4 School of Public Health and Medicine, University of North Carolina, Chapel Hill, NC, USA,
5 School of Medicine, University of California San Francisco, San Francisco, CA, USA,
6 Inhalation Toxicology Research Institute, Albuquerque, NM, USA,
7 California State Health Department, Berkeley, CA, USA,
8 Genetics Laboratory, University of Vermont, Burlington, VT, USA and
9 Institute of Occupational Medicine, Yanshan Petrochemical Products Corporation, Yanshan, People's Republic of China
While 1,3-butadiene is carcinogenic in rodents, cancer causation in humans is less certain. We examined a spectrum of genotoxic outcomes in 41 butadiene polymer production workers and 38 non-exposed controls, in China, to explore the role of butadiene in human carcinogenesis. Because in vitro studies suggest that genetic polymorphisms in glutathione S-transferase enzymes influence genotoxic effects of butadiene, we also related genotoxicity to genetic polymorphisms in GSTT1 and GSTM1. Among butadiene-exposed workers, median air exposure was 2 p.p.m. (6 h time-weighted average), due largely to intermittent high level exposures. Compared with unexposed subjects, butadiene-exposed workers had greater levels of hemoglobin N-(2,3,4-trihydroxybutyl)valine (THBVal) adducts (P < 0.0001) and adduct levels tended to correlate, among butadiene-exposed workers, with air measures (P = 0.03). Butadiene-exposed workers did not differ, however, from unexposed workers with respect to frequency of uninduced or diepoxybutane-induced sister chromatid exchanges, aneuploidy as measured by fluorescence in situ hybridization of chromosomes 1, 7, 8 and 12, glycophorin A variants or lymphocyte hprt somatic mutation. Also among the exposed, greater THBVal levels were not associated with increases in uninduced sister chromatid exchanges, aneuploidy, glycophorin A or hprt mutations. Butadiene-exposed workers had greater lymphocyte (P = 0.002) and platelet counts (P = 0.07) and lymphocytes as a percentage of white blood cells were moderately correlated with greater THBVal levels (Spearman's 
= 0.32, P = 0.07). Among butadiene-exposed workers, neither GSTM1 nor GSTT1 genotype status predicted urinary mercapturic acid butanediol formation, THBVal adducts, uninduced sister chromatid exchanges, aneuploidy or mutations in the glycophorin A or hprt genes. Overall, the study demonstrated exposure to butadiene in these workers, by a variety of short-term and long-term measures, but did not show specific genotoxic effects, at the chromosomal or gene levels, related to that exposure.
Abbreviations: BD, 1,3-butadiene; B-diol, 3-butene-1,2-diol; BDO, 3,4-epoxy-1-butene; BDO2, 1,2,3,4-diepoxybutane; BDO-diol, 3,4-epoxy-1,2-butanediol; CE, cloning efficiencies; DMF, dimethyl formamide; FBS, fetal bovine serum; FISH, fluorescence in situ hybridization; GPA, glycophorin A; M-1, mercapturic acid butanediol; M-2, mercapturic acid butenol; PFPTH, pentafluorophenyl thiohydantoin; SCE, sister chromatid exchange; THBVal, N-(2,3,4-trihydroxybutyl)valine; WBC, total leukocyte count.
10 To whom correspondence should be addressed Email: hayesr{at}exchange.nih.gov
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