Excretion of metabolites in urine and faeces from rats dosed with the heterocyclic amine, 2-amino-9 H-pyrido[2,3- b]indole (AαC)

Abstract

2-amino-9 H-pyrido[2,3- b]indole (AαC) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems AαC can be formed by pyrolysing either tryptophan or proteins of animal or vegetable origin. In the present study, the in vivo metabolism of AαC in rats was investigated. Rats were dosed with tritium labelled AαC. Urine and faeces were collected over three days. The metabolites of AαC were characterised by HPLC-MS and quantified by liquid scintillation counting. Conjugated metabolites were characterised by enzymatic hydrolyses with β-Glucuronidase or arylsulfatase. The data showed that the metabolic pattern of AαC was similar in all rats. About 55% of the dose was excreted in urine and faeces during 72 h and the major amount of AαC metabolites (31%) was excreted during the first 24 h. In addition to a small amount of unmetabolised AαC seven conjugated metabolites were characterised. Three minor metabolites were characterised as AαC- N 2-glucuronide and glucuronic acid conjugates of 3-OH-AαC and 6-OH-AαC. Four metabolites were all characterised as sulphuric acid conjugates and accounted for the largest amount of metabolites excreted in urine. The two major sulphuric acid conjugates were identified as AαC-3- O-sulfate and AαC-6- O-sulfate, while the minor sulphuric acid conjugates were proposed to be other O-sulfonated metabolites. In faeces only AαC was excreted and accounted for about 12% of dose during the first 24 hours. Any activated metabolites of AαC were not detected in rat urine or faeces. In future accumulation or binding of AαC to macromolecules such as DNA and proteins has to be studied.