title: Glutathione mutagenesis in Salmonella typhimurium is a gamma-glutamyltranspeptidase-enhanced process involving active oxygen species.
abstract: Reduced glutathione (GSH) is mutagenic in Salmonella in the presence of gamma-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.
mesh_terms: D002374:Catalase / Q000494:pharmacology; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism / Q000633:toxicity*; D006735:Horseradish Peroxidase / Q000494:pharmacology; D009153:Mutagens; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000502:physiology*
chemical_list: D009153:Mutagens; D006735:Horseradish Peroxidase; D002374:Catalase; D013482:Superoxide Dismutase; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D010100:Oxygen