Mutagenicity of 1,3-butadiene and its epoxide metabolites in human TK6 cells and in splenic T cells isolated from exposed B6C3F1 mice.
The mutagenic potential of 1,3-butadiene and its epoxide metabolites have been measured in a human lymphoblastoid cell line (TK6) and in splenic T cells from exposed B6C3F1 mice. TK6 cells were exposed for 24 h to 0-400 microM 1,2-epoxybutene, 0-800 microM 3,4-epoxy-1,2-butanediol or 0-6 microM diepoxybutane and plated to measure the frequencies of mutations at the hprt and tk loci. All three metabolites were mutagenic at both loci, but diepoxybutane was active at concentrations 100 times lower than epoxybutene or epoxybutanediol. Mice exposed to 625 ppm butadiene for two weeks had an average hprt mutation frequency of 6.2 x 10(-6) in splenic T cells, whereas that in controls was 1.2 x 10(-6). In mice given three daily intraperitoneal doses of epoxybutene at 60, 80 and 100 mg/kg or diepoxybutane at 7, 14 and 21 mg/kg, the average hprt frequencies were 5.4, 4.1 and 8.6 x 10(-6) in those given epoxybutene and 4.6, 9.4 and 13 x 10(-6) in those treated with diepoxybutane. DNA sequencing revealed that 50% of the mutations induced in vivo by butadiene, epoxybutene and diepoxybutane were transition and transversion mutations at AT and GC base-pairs and 50% were frameshift mutations. The mutational spectra obtained are very similar to that produced by ethylene oxide, suggesting that these epoxides act through a similar mechanism.
Cochrane
J E
JE
Department of Pathology, University of North Carolina at Chapel Hill.
Skopek
T R
TR
D000818:Animals; D002070:Butadienes / Q000633:toxicity*; D002478:Cells, Cultured; D004852:Epoxy Compounds / Q000633:toxicity; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D013601:T-Lymphocytes / Q000187:drug effects
D002070:Butadienes; D004852:Epoxy Compounds; D009153:Mutagens; C024370:3,4-epoxy-1-butene; C007366:diepoxybutane; C031763:1,3-butadiene