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Mutagenicity of a glutathione conjugate of butadiene diepoxide.

ABSTRACT: 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.

SUBMITTER: Cho SH

PROVIDER: S-EPMC3848503 | biostudies-other | 2010 Oct

REPOSITORIES: biostudies-other

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Mutagenicity of a glutathione conjugate of butadiene diepoxide.

Cho Sung-Hee SH Loecken Elisabeth M EM Guengerich F Peter FP

Chemical research in toxicology 20100929 10

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 ...[more]

PMID: 20879737

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Conjugation of butadiene diepoxide with glutathione yields DNA adducts in vitro and in vivo.

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