Abstract
2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeAαC can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in vivo metabolism of MeAαC in rats was investigated. Rats were dosed with tritium-labeled MeAαC, and urine and feces were collected over 3 days. The metabolites of MeAαC were identified by high performance liquid chromatography-mass spectrometry and quantified by liquid scintillation counting. Conjugated metabolites were characterized by enzymatic hydrolyzes with β-glucuronidase or arylsulfatase. The data showed that the metabolic pattern of MeAαC was similar in all rats. About 65% of the dose was excreted in urine and feces, and the major amount of MeAαC-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 MeAαC and two phase I metabolites, 6-OH-MeAαC and 7-OH-MeAαC, the following conjugated metabolites were identified: MeAαC-N2-glucuronide, AαC-3-CH2O-glucuronide, 3-carboxy-AαC and 3-carboxy-AαC-glucuronide, and sulfate and glucuronide conjugates of 6-OH-MeAαC and 7-OH-MeAαC. Also, a large amount of a rather unstable compound proposed to be of MeAαC-N1-glucuronide was found. About 21% of the dose was excreted in feces during the first 24 h, and MeAαC and 7-OH-MeAαC were the only compounds identified in feces. Any activated metabolites of MeAαC were not detected in rat urine or feces.
Footnotes
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↵1 Abbreviations: AαC, 2-amino-9H-pyrido[2,3-b]indole; HPLC, high performance liquid chromatography; MeAαC, 2-amino-3-methyl-9H-pyrido[2,3-b]indole; MeIQx, 2-amino-4,8-dimethylimidazo[4,5-f]quinoxaline; PCB, Aroclor 1254 (polychlorinated biphenyl); Rt, retention time.
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This study has been carried out with financial support from the commission of the European communities, specific RTD program “Quality of life and management of living resources” QLK1-CT99-01197, Heterocyclic amines in cooked foods—Role in human health. It does not necessarily reflect its views and in no way anticipates the commission's future policy in this area.
- Received November 3, 2003.
- Accepted March 12, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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