Genotoxic markers among butadiene polymer workers in 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 butadie ne polymer production workers and 38 non-exposed controls, in China, to exp lore the role of butadiene in human carcinogenesis. Because in vitro studie s suggest that genetic polymorphisms in glutathione S-transferase enzymes i nfluence genotoxic effects of butadiene, we also related genotoxicity to ge netic polymorphisms in GSTT1 and GSTM1. Among butadiene-exposed workers, me dian air exposure was 2 p.p.m. (6 h time-weighted average), due largely to intermittent high level exposures. Compared with unexposed subjects, butadi ene-exposed workers had greater levels of hemoglobin N-(2,3,4-trihydroxybut yl)valine (THBVal) adducts (P < 0.0001) and adduct levels tended to correla te, among butadiene-exposed workers, with air measures (P = 0.03). Butadien e-exposed workers did not differ, however, from unexposed workers with resp ect to frequency of uninduced or diepoxybutane-induced sister chromatid exc hanges, aneuploidy as measured by fluorescence in situ hybridization of chr omosomes 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, glycop horin 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 phi = 0.32, P = 0.07). Among butadiene-exposed workers, neithe r GSTM1 nor GSTT1 genotype status predicted urinary mercapturic acid butane diol formation, THBVal adducts, uninduced sister chromatid exchanges, aneup loidy or mutations in the glycophorin A or hprt genes. Overall, the study d emonstrated exposure to butadiene in these workers, by a variety of short-t erm and long-term measures, but did not show specific genotoxic effects, at the chromosomal or gene levels, related to that exposure.