title: Genotoxic markers among butadiene polymer workers in China.
abstract: 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 phi = 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.
authors.affiliation: Occupational Studies Branch, National Cancer Institute, Bethesda, MD, USA. hayesr@exchange.nih.gov
authors.forename: R B
authors.initials: RB
authors.lastname: Hayes
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Yin
authors.forename: J A
authors.initials: JA
authors.lastname: Swenberg
authors.forename: L
authors.initials: L
authors.lastname: Xi
authors.forename: J
authors.initials: J
authors.lastname: Wiencke
authors.forename: W E
authors.initials: WE
authors.lastname: Bechtold
authors.forename: M
authors.initials: M
authors.lastname: Yao
authors.forename: N
authors.initials: N
authors.lastname: Rothman
authors.forename: R
authors.initials: R
authors.lastname: Haas
authors.forename: J P
authors.initials: JP
authors.lastname: O'Neill
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Wiemels
authors.forename: M
authors.initials: M
authors.lastname: Dosemeci
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: M T
authors.initials: MT
authors.lastname: Smith
mesh_terms: D000328:Adult; D015415:Biomarkers; D002070:Butadienes / Q000633:toxicity*; D002869:Chromosome Aberrations; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D016273:Occupational Exposure; D012854:Sister Chromatid Exchange; D014633:Valine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002070:Butadienes; D006454:Hemoglobins; D009153:Mutagens; C101918:N-(2,3,4-trihydroxybutyl)valine; D005982:Glutathione Transferase; D014633:Valine