Mutagenic activity of various chemicals in Salmonella strain TA100 and glutathione-deficient derivatives. On the role of glutathione in the detoxification or activation of mutagens inside bacterial cells.
Several mutants with decreased levels of reduced glutathione (GSH) were isolated from the sensitive mutagen tester strain Salmonella typhimurium TA100 after treatment with u.v. and selection for resistance to N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) and its methyl analogue MNNG. Estimation of the GSH concentration and GSH S-transferase activity in extracts of these strains and of TA100 indicates that the GSH- derivatives contain 10-30% of the GSH level found in TA100, and that they exhibit normal GSH S-transferase activity. The mutagenic activities of 7 chemicals, namely, MNNG, ENNG, 1,2-dibromoethane (DBE), 1-chloro-2,4-dinitrobenzene (CDNB), styrene-7,8-oxide (STOX), N-ethyl-N-nitrosourea (ENU) and methyl methane sulphonate (MMS) were compared in TA100 and in one representative GSH- strain, denominated NG-57. MNNG, ENNG, DBE and CDNB are potent to extremely potent mutagens in TA100, but induce very low levels of His+ mutants in NG-57. Pretreatment of NG-57 with 1 mM GSH (partially) restores the mutant yields to the levels usually found in TA100. The mutagenic activities of STOX, ENU and MMS are similar in both strains. These results support some previous findings, namely that ENNG, MNNG and DBE, but not ENU are activated to mutagens inside the test bacteria, and also suggest that CDNB is activated by bacterial GSH. The latter finding is in contrast with the current view that CDNB is detoxified by GSH, as is also presently evidenced by a strong reduction of the compound's mutagenicity in the presence of extracts of rat liver, which contains GSH and GSH S-transferase activity. The results with STOX indicate that GSH plays in bacteria a much less important role in the detoxification of xenobiotics than in mammalian tissue, presumably due to a much lower GSH S-transferase activity in the first organism.
D001711:Biotransformation; D005978:Glutathione / Q000502:physiology*; D005982:Glutathione Transferase / Q000032:analysis; D008658:Inactivation, Metabolic; D009153:Mutagens / Q000378:metabolism*; D012475:Salmonella / Q000187:drug effects / Q000378:metabolism*
D009153:Mutagens; D005982:Glutathione Transferase; D005978:Glutathione