Absorption of 3-amino-1-methyl-5H-pyrido[4,3-b]indole, a mutagen-carcinogen present in tryptophan pyrolysate, from the gastro-intestinal tract in the rat.

Abstract

The absorption characteristics of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), a mutagen-carcinogen present in tryptophan pyrolysate, in the gastrointestinal tract was investigated in Wistar male rats by an in situ loop technique. Trp-P-2, a weak base with a pKa of 8.2, was poorly lipophilic below pH 5 and therefore the gastric absorption was negligible at pH 1.1 and 3.0. On the other hand, this compound was rapidly absorbed from the small intestine even at pH 4.0 and the absorption was even faster at higher pH where the unionized fraction increases. The absorption from the large intestine was also rapid. Although the intestine is one of the major metabolic organs for ingested materials, metabolism of Trp-P-2 by the scraped mucosa of the small intestine was slow in comparison with that in the liver. Formation of direct-acting mutagens (towards S. typhimurium TA98) associated with the metabolism was also much slower in the small-intestinal mucosa than in the liver. These results suggest that this mutagen is activated mainly after being incorporated into the liver, and are consistent with the liver-specific carcinogenicity of Trp-P-2 in rats.