Mutagenicity spectra in Salmonella typhimurium strains of glutathione, L-cysteine and active oxygen species.
Glutathione and L-cysteine, in the presence of rat kidney post-mitochondrial supernatant (S9) fraction, and various forms of active oxygen were investigated for mutagenicity in seven his- strains of Salmonella typhimurium. Glutathione and L-cysteine showed qualitatively and quantitatively virtually identical mutagenic activities. The number of mutants induced in strain TA97 was 3-4 times higher than in TA100, the strain in which the mutagenicity was originally detected. Mutagenic effects were also observed in strains TA92, TA102 and TA104, but not in TA1535 and TA1537. Hydrogen peroxide, superoxide and glucose/glucose oxidase in the presence and absence of kidney S9 fraction showed pronounced mutagenic effects in strains TA104 and TA102. Additionally, weak mutagenic effects were observed in TA100, while the remaining strains, including TA97, were not responsive. These mutagenicity spectra suggest that the mutagenic species formed from glutathione and L-cysteine are similar, if not identical, and are different from hydrogen peroxide, superoxide and other oxygen species derived from them. Further support for this notion was given when it was observed that catalase did not affect the mutagenicity of glutathione and that superoxide dismutase showed a significant effect only when used in milligram quantities. This study shows that mutagenicity spectra may be useful in the elucidation of activation pathways. Furthermore, it is interesting to note that all the compounds and preparations showing a positive response in the Ames test in the present study occur endogenously in organisms: glutathione, L-cysteine, hydrogen peroxide, superoxide, glucose, glucose oxidase and kidney S9 fraction (which was mutagenic in several strains).
Glatt
H
H
Institute of Toxicology, University of Mainz, FRG.
D000818:Animals; D001711:Biotransformation; D002374:Catalase / Q000494:pharmacology; D003545:Cysteine / Q000378:metabolism / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism / Q000633:toxicity*; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism / Q000633:toxicity
D009153:Mutagens; D013481:Superoxides; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D003545:Cysteine; D010100:Oxygen