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

Toshikiro Kimura, Taiji Nakayama, Yuji Kurosaki, Yasuko Suzuki, Sakae Arimoto, Hikoya Hayatsu

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 directacting 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.

Original languageEnglish
Pages (from-to)272-277
Number of pages6
JournalJapanese Journal of Cancer Research
Volume76
Issue number4
Publication statusPublished - Apr 1985

Fingerprint

Mutagens
Carcinogens
Gastrointestinal Tract
Liver
Small Intestine
Large Intestine
Intestinal Mucosa
Intestines
3-amino-1-methyl-5H-pyrido(4,3-b)indole
Wistar Rats
Mucous Membrane

Keywords

  • Biliary excretion
  • Gastrointestinal absorption
  • Mutagenic activation
  • Portal pathway
  • Trp-P-2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Absorption of 3-amino-1-methyl-5H-pyrido[4,3-b]indole, a mutagen-carcinogen present in tryptophan pyrolysate, from the gastrointestinal tract in the rat. / Kimura, Toshikiro; Nakayama, Taiji; Kurosaki, Yuji; Suzuki, Yasuko; Arimoto, Sakae; Hayatsu, Hikoya.

In: Japanese Journal of Cancer Research, Vol. 76, No. 4, 04.1985, p. 272-277.

Research output: Contribution to journalArticle

@article{ef712dd0c4ba43fabf0b72c7481a074c,
title = "Absorption of 3-amino-1-methyl-5H-pyrido[4,3-b]indole, a mutagen-carcinogen present in tryptophan pyrolysate, from the gastrointestinal 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 directacting 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.",
keywords = "Biliary excretion, Gastrointestinal absorption, Mutagenic activation, Portal pathway, Trp-P-2",
author = "Toshikiro Kimura and Taiji Nakayama and Yuji Kurosaki and Yasuko Suzuki and Sakae Arimoto and Hikoya Hayatsu",
year = "1985",
month = "4",
language = "English",
volume = "76",
pages = "272--277",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Absorption of 3-amino-1-methyl-5H-pyrido[4,3-b]indole, a mutagen-carcinogen present in tryptophan pyrolysate, from the gastrointestinal tract in the rat

AU - Kimura, Toshikiro

AU - Nakayama, Taiji

AU - Kurosaki, Yuji

AU - Suzuki, Yasuko

AU - Arimoto, Sakae

AU - Hayatsu, Hikoya

PY - 1985/4

Y1 - 1985/4

N2 - 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 directacting 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.

AB - 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 directacting 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.

KW - Biliary excretion

KW - Gastrointestinal absorption

KW - Mutagenic activation

KW - Portal pathway

KW - Trp-P-2

UR - http://www.scopus.com/inward/record.url?scp=0021839194&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021839194&partnerID=8YFLogxK

M3 - Article

VL - 76

SP - 272

EP - 277

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 4

ER -