MICROSOMAL METABOLISM OF THE FOOD MUTAGEN 2-AMINO-3,4,8-TRIMETHYL-3H-IMIDAZO[4,5-F]-QUINOXALINE TO MUTAGENIC METABOLITES

Heterocyclic aromatic amines are formed in the crust of meat during ordinary cooking. These aromatic amines are potent bacterial mutagens and also potent rodent carcinogens. 2-Amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (DiMeIQx)) is one of the more abundant heterocyclic aromatic amines, accounting for similar to 20% of the mutagenic material found in cooked meat. DiMeIQx is metabolically activated, by hepatic microsomes from PCB treated rats, to two major and three minor metabolites. One major and one minor metabolite were identified as 2-hydroxyamino-3,4,8-trimethyl-3H-imidazo[4,5-f] quinoxaline and 3,4,8-trimethyl-2nitro-3H-imidazo[4,5-f]quinoxaline, respectively, confirmed by comparison of HPLC retention times, and UV and mass spectra of synthetic standards. Both metabolites were mutagenic in Salmonella typhimurium TA98 without metabolic activation. The other major metabolite was identified as 2-amino-8-hydroxymethyl-3,4-dimethyl-3H-quinoxaline by mass and NMR spectral analysis. The two remaining minor metabolites were identified as the 2-hydroxyamino- and 2-nitro- derivatives of 2-amino-8-hydroxymethyl-3,4-dimethyl-3H-imidazo[4,5-f]qui by UV and mass spectral analysis. Both of these metabolites were mutagenic in S.typhimurium TA98 without metabolic activation.