TY - JOUR
T1 - Glutathione mutagenesis in salmonella typhimurium is a γ-glutamyltranspeptidase-enhanced process involving active oxygen species
AU - Stark, Avishay Abraham
AU - Zeiger, Errol
AU - Pagano, Dennis A.
N1 - Funding Information:
We are grateful to Dr Y.Aharooowitz, Tel-Aviv University, for helpful discussions and to Mr E.Reuveni and Ms Y.Lifshitz for technical assistance. This work was supported in part by a grant from the Moise and Frida Eskenasy Institute for Cancer Research. A part of this work was carried out when A.-A.Stark was a Visiting Scientist at CGTB, NIEHS.
PY - 1988/5
Y1 - 1988/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0023917659&partnerID=8YFLogxK
U2 - 10.1093/carcin/9.5.771
DO - 10.1093/carcin/9.5.771
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AN - SCOPUS:0023917659
SN - 0143-3334
VL - 9
SP - 771
EP - 777
JO - Carcinogenesis
JF - Carcinogenesis
IS - 5
ER -