Metabolic activation of a tryptophan pyrolysis product, 3-amino-1-methyl-5H-pyrido[4,3-b]indole(TRP-P-2) by isolated rat liver nuclei.

The metabolic activation of a tryptophan pyrolysis product, 3-amino-1-methyl-5H-pyrido[4,3-b]indole(Trp-P-2), by rat liver nuclei was studied. Nuclei from the livers of rats treated with polychlorinated biphenyl (PCB) or 3-methylcholanthrene (MC) showed high mutagenic activity with Trp-P-2 in the Ames test, but activities with nuclei of untreated or phenobarbital (PB)-treated rat livers were quite low. The formation of N-hydroxy-Trp-P-2 by nuclei of PCB- or MC-treated rat livers was greater than that by nuclei of untreated or PB-treated rat livers. Similar results were observed with microsomes, which suggests that Trp-P-2 is metabolized by the same type of monoxygenase system in nuclei as in microsomes.