Glutathione transferase-mediated and non-enzymatic activation and detoxication of the N-hydroxy derivative of Trp-P-2, a potent pyrolysate promutagen.
Glutathione (GSH) transferase-mediated and non-enzymatic activation and detoxication of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-OH-Trp-P-2) were studied in vitro. N-OH-Trp-P-2 is an active metabolite of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), a mutagenic and carcinogenic heterocyclic amine. The enzymatic GSH conjugation with N-OH-Trp-P-2 was catalysed by rat-liver GSH transferase and a rat-liver cytosol fraction to form three conjugates (CH-1, CH-2 and CH-3). The mutagenicities of the GSH conjugates were studied by using Salmonella typhimurium TA98 as the tester strain. The GSH conjugates except for CH-3 were completely detoxicated products, but CH-3 was found to be a more potent mutagen than N-OH-Trp-P-2. The mutagenicity of CH-3 seemed to be due to the direct action of the conjugate, but not to N-OH-Trp-P-2 formed from it.
D000818:Animals; D001711:Biotransformation; D002243:Carbolines / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D008658:Inactivation, Metabolic; D007211:Indoles / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D009152:Mutagenicity Tests; D051381:Rats; D011919:Rats, Inbred Strains
D002243:Carbolines; D007211:Indoles; C027210:3-hydroxyamino-1-methyl-5H-pyrido(4,3-b)indole; D005982:Glutathione Transferase; D005978:Glutathione