Metabolic activation of Trp-P-2, a mutagenic amine from tryptophan-pyrolysate, by liver microsomes from 3-methylcholanthrene-responsive and non-responsive mice

Abstract

1. The metabolic activation of a tryptophan pyrolysate, Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole), was studied using liver microsomes from mice of 3-methylcholanthrene-responsive, C57BL/6N (B6) strain and non-responsive, DBA/2N (D2) strain.

2. The formation of N-hydroxy-Trp-P-2 (3-hydroxylamino-1-methyl-5H-pyrido-[4,3-b]indole) by hepatic microsomes was markedly increased by the pretreatment with 3-methylcholanthrene in B6 mice, but not in D2 mice.

3. The same treatment increased the activity to convert Trp-P-2 to a mutagen(s) in the Salmonella/microsome test system in B6 mice, but not in D2 mice.

4. The formation of N-hydroxy-Trp-P-2 corresponded with the increase in the number of the revertants, and with the activities of aromatic hydrocarbon hydroxylase and biphenyl 2-hydroxylase.

5. Addition of α-naphthoflavone to microsomes from control and 3-methyl-cholanthrene-treated B6 mice effectively decreased the activities to convert Trp-P-2 to a mutagen(s) and to N-hydroxylate Trp-P-2.

6. These results indicate that N-hydroxy-Trp-P-2 is a proximate or ultimate mutagenic principle of Trp-P-2.