Isolation and characterization of active metabolites of tryptophan-pyrolysate mutagen, TRP-P-2, formed by rat liver microsomes.
The mutagenic compound derived from the pyrolysis of tryptophan, 3-amino-1-methyl-5H-pyrido-[4,3b]indole (Trp-P-2) was metabolized by rat liver microsomes to more than four metabolites, separable by high performance liquid chromatography. Among these metabolites, two metabolites, M-3 and M-4 were directly active in increasing the frequency of mutation in Salmonella typhimurium TA98. Treatments of rats with polychlorinated biphenyl (PCB) or 3-methylcholanthrene dramatically induced the activity of liver microsomes to form these active metabolites, while treatment with phenobarbital was without effect. A major active metabolite (M-3) formed the pentacyano-ammine ferroate, which is known to be formed by reaction of sodium pentacyano-ammine ferroate with some hydroxylamines. Further this metabolite was oxidized to the minor active metabolite (M-4) with potassium ferricyanide or gamma-manganese dioxide, and was reduced back to Trp-P-2 with titanium trichloride. These results indicated that the major active metabolite of Trp-P-2, which is formed by cytochrome P-450, is the 3-hydroxyamino derivative.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002243:Carbolines / Q000302:isolation & purification* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D007211:Indoles / Q000302:isolation & purification*; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism*; D009153:Mutagens / Q000302:isolation & purification* / Q000378:metabolism; D010084:Oxidation-Reduction; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D051381:Rats; D013057:Spectrum Analysis; D014364:Tryptophan / Q000031:analogs & derivatives*
D002243:Carbolines; D007211:Indoles; D009153:Mutagens; D008748:Methylcholanthrene; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D014364:Tryptophan; D011078:Polychlorinated Biphenyls