QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Frederiksen, H. Articles by Frandsen, H. Search for Related Content PubMed PubMed Citation Articles by Frederiksen, H. Articles by Frandsen, H.

IDENTIFICATION OF METABOLITES IN URINE AND FECES FROM RATS DOSED WITH THE HETEROCYCLIC AMINE, 2-AMINO-3-METHYL-9H-PYRIDO[2,3-b]INDOLE (MeAC)

Institute of Food Safety and Nutrition, Danish Veterinary and Food Administration, Søborg, Denmark

2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAC) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeAC can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in vivo metabolism of MeAC in rats was investigated. Rats were dosed with tritium-labeled MeAC, and urine and feces were collected over 3 days. The metabolites of MeAC were identified by high performance liquid chromatography-mass spectrometry and quantified by liquid scintillation counting. Conjugated metabolites were characterized by enzymatic hydrolyzes with ß-glucuronidase or arylsulfatase. The data showed that the metabolic pattern of MeAC was similar in all rats. About 65% of the dose was excreted in urine and feces, and the major amount of MeAC-metabolites was excreted during the first 24 h. Thirty-four percent of the dose was found in the rat urine samples collected to 24 h. In addition to unmetabolized MeAC and two phase I metabolites, 6-OH-MeAC and 7-OH-MeAC, the following conjugated metabolites were identified: MeAC-N²-glucuronide, AC-3-CH₂O-glucuronide, 3-carboxy-AC and 3-carboxy-AC-glucuronide, and sulfate and glucuronide conjugates of 6-OH-MeAC and 7-OH-MeAC. Also, a large amount of a rather unstable compound proposed to be of MeAC-N1-glucuronide was found. About 21% of the dose was excreted in feces during the first 24 h, and MeAC and 7-OH-MeAC were the only compounds identified in feces. Any activated metabolites of MeAC were not detected in rat urine or feces.