Glutathione mutagenesis in salmonella typhimurium is a γ-glutamyltranspeptidase-enhanced process involving active oxygen species

Avishay Abraham Stark*, Errol Zeiger, Dennis A. Pagano

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Reduced glutathione (GSH) is mutagenic in Salmonella in the presence of γ-glutamyltranspeptidase (GGT), with the highest response obtained in strain TA102. Reduced cysteinylglycine, one of the products of GGT metabolism of GSH, is mutagenic in the absence of GGT. In strain TA102, GSH mutagenesis was dependent on molecular oxygen, enhanced by iron, inhibited by EDTA, desferrioxamine mesylate, mannitol, butylated hydroxyanisole, peroxidase and catalase, but not by superoxide dismutase. Binding of GSH or its GGT-dependent metabolites to DNA in vitro was not detected. This is consistent with a model of an indirect mechanism of mutagenesis, i.e. cleavage of GSH by GGT, followed by facile auto-oxidation of the resulting cysteinylglycine, with the production of free radicals which lead to the (pen)ultimate mutagen, H2O2.

Original languageEnglish
Pages (from-to)771-777
Number of pages7
JournalCarcinogenesis
Volume9
Issue number5
DOIs
StatePublished - May 1988

Funding

FundersFunder number
Moise and Frida Eskenasy Institute for Cancer Research

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