Mutagenicity of a glutathione conjugate of butadiene diepoxide.

Cho SH, Loecken EM, Guengerich FP
Chem Res Toxicol. 2010 23 (10): 1544-6

PMID: 20879737 · PMCID: PMC3848503 · DOI:10.1021/tx100304f

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.

MeSH Terms (9)

Animals Butadienes DNA Epoxy Compounds Glutathione Glutathione Transferase Mutagenicity Tests Rats Salmonella typhimurium

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