Mutagenicity of thiol compounds in Escherichia coli WP2 tester strain IC203, deficient in OxyR: effects of S9 fractions from rat liver and kidney.
Low doses of L-cysteine (CYS), cysteinyl-glycine (CYSGLY) and reduced glutathione (GSH) activated by gamma-glutamyl transpeptidase (GGT) were mutagenic in strain IC203 (oxyR), whereas higher doses were required to observe a weak mutagenicity in the oxyR+ strain WP2 uvrA/pKM101 (denoted IC188). This indicates that thiol mutagenesis is suppressed by OxyR-regulated antioxidant defenses and confirms its oxidative character. The mutagenesis by low doses of CYS, CYSGLY and GSH + GGT detected in IC203 was abolished by rat liver S9, through the activity of catalase, as well as by the metal chelator diethyldithiocarbamate (DETC), supporting the dependence of this mutagenesis on H2O2 production, probably in thiol autoxidation reactions in which transition metals are involved. Surprisingly, low DETC concentrations greatly potentiate the mutagenicity of low CYS doses. Mutagenesis by high doses of CYS and CYSGLY occurred in both IC203 and IC188 in the presence of liver S9, and was resistant to inhibition by catalase, although it was prevented by DETC. Mutagenesis by GSH activated by rat kidney S9, rich in GGT, was detected in IC203 and IC188 only at high doses since catalase and glutathione peroxidase, both present in kidney S9, might inhibit its induction by low GSH doses. In the presence of liver S9, almost deficient in GGT, GSH was not mutagenic. The mutagenicity of a high GSH dose occurring in the presence either of GGT plus liver S9 or of kidney S9 was weakly prevented by DETC.
Martínez
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Instituto de Investigaciones Citológicas, Fundación-Valenciana de Investigaciones Biomédicas, Spain.
Urios
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Blanco
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D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003545:Cysteine / Q000633:toxicity; D004268:DNA-Binding Proteins; D004151:Dipeptides / Q000633:toxicity; D004050:Ditiocarb / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins; D005978:Glutathione / Q000378:metabolism / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000633:toxicity; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D016296:Mutagenesis; D009152:Mutagenicity Tests / Q000379:methods*; D016877:Oxidants / Q000633:toxicity; D010084:Oxidation-Reduction; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000633:toxicity*; D014020:Tissue Extracts / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000633:toxicity
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D004151:Dipeptides; D029968:Escherichia coli Proteins; D016877:Oxidants; D012097:Repressor Proteins; D013438:Sulfhydryl Compounds; D014020:Tissue Extracts; D014157:Transcription Factors; C499299:oxyR protein, E coli; C028505:cysteinylglycine; D020122:tert-Butylhydroperoxide; D004050:Ditiocarb; D006861:Hydrogen Peroxide; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D003545:Cysteine