Metabolism of the dietary carcinogen TRP-P-1 in rats

The heterocyclic amine 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole (Trp-P-1) was administered as a single oral dose to conventional, bile-fistulated and germ-free rats. There was rapid excretion of Trp-P-1 and its metabolites via the bile, urine and feces. The pattern of metabolites did not differ markedly between the three excretory routes. While there was considerable excretion of unmetabolized Trp-P-1, at the dose level used, there was also extensive metabolism to primary ring-hydroxylated and N-acetylated metabolites which were polar enough to be excreted without undergoing conjugation reactions. Four of the metabolites exhibited mutagenic activity towards Salmonella typhimurium TA98 in the presence of S9 mix. However, all showed a lower mutagenicity than the parent compound. Studies with the bile-fistulated animals indicated that enterohepatic circulation was occurring with Trp-P-1. The intestinal microflora did not appear to have a major role to play in the metabolism of this heterocyclic amine but they did lead to the formation of 'bound fecal residues' in the gut of the conventional animals.