Interactions between the active metabolite of tryptophan pyrolysate mutagen, N-hydroxy-Trp-P-2, and lipids: the role of lipid peroxides in the conversion of N-hydroxy-Trp-P-2 to non-reactive forms.

The interactions between lipids and the mutagenic active metabolite of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-hydroxy-Trp-P-2), were studied. Oleic acid showed an inhibitory effect on the formation of this active metabolite mainly by inhibition of hepatic microsomal oxidation systems. On the other hand, microsomal lipids from rat liver and commercial pig liver lecithin diminished the amount of N-hydroxy-Trp-P-2 without inhibiting the metabolism of Trp-P-2. The direct reaction of these lipids with N-hydroxy-Trp-P-2 was disclosed by experiments using N-hydroxy-Trp-P-2 and lipids without microsomes. Furthermore, the participation of lipid peroxides in this reaction was suggested by a linear relationship between the concentrations of the conjugated diene of lipids and the disappearance of N-hydroxy-Trp-P-2. When [3H]N-hydroxy-Trp-P-2 was incubated in the presence of pig liver lecithin, the polar products which were not formed in the incubation without lipids were newly detected by thin-layer chromatography (TLC) analysis.