STRUCTURAL ELUCIDATION OF A MUTAGENIC METABOLITE OF 3-AMINO-1-METHYL-5H-PYRIDO[4,3-B]INDOLE

Abstract

Metabolic activation of a tryptophan pyrolysate, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) [a carcinogenic substance found in many foods] by rat liver microsomes was studied. Trp-P-2 was converted to at least 4 metabolites (M-1 to M-4), which were separable by HPLC [high pressure liquid chromatography] or TLC. The major metabolite (M-3) was extremely mutagenic to Salmonella typhimurium TA 98 in the absence of activating enzymes and the activity accounted for almost all mutagenic effects of Trp-P-2. Metabolite M-3 was identified as 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole by mass spectrometry and by conversion to the 4-chloro derivative of Trp-P-2 by treatment with HCl. The latter compound was identified by NMR and mass spectrometry.