Mutagenicity of a glutathione conjugate of butadiene diepoxide.
The mutagenicity and carcinogenicity of the important commodity chemical 1,3-butadiene are attributed to the epoxide products. We confirmed our previous work showing that expression of rat glutathione (GSH) transferase 5-5 enhances the mutagenicity of butadiene diepoxide in Salmonella typhimurium TA1535. A GSH-butadiene diepoxide conjugate was isolated and fully characterized by mass spectrometry and nuclear magnetic resonance as S-(2-hydroxy-3,4-epoxybutyl)GSH. The conjugate had a t(½) of 2.6 h (pH 7.4, 37 °C) and was considerably more mutagenic than butadiene diepoxide or monoepoxide in S. typhimurium. We propose that the GSH conjugate may be a major species involved in butadiene genotoxicity, not a detoxication product.
Cho
Sung-Hee
SH
Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
Loecken
Elisabeth M
EM
Guengerich
F Peter
FP
D000818:Animals; D002070:Butadienes / Q000737:chemistry*; D004247:DNA / Q000378:metabolism; D004852:Epoxy Compounds / Q000737:chemistry* / Q000633:toxicity; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000633:toxicity; D005982:Glutathione Transferase / Q000378:metabolism; D009152:Mutagenicity Tests; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000378:metabolism
D002070:Butadienes; D004852:Epoxy Compounds; C578346:S-(2-hydroxy-3,4-epoxybutyl)glutathione; D004247:DNA; D005982:Glutathione Transferase; D005978:Glutathione; C031763:1,3-butadiene