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

Heterocyclic aromatic amines are formed in the crust of meat during or dinary cooking. These aromatic amines are potent bacterial mutagens an d also potent rodent carcinogens. Amino-3,4,8-trimethyl-3H-imidazo[4,5 -f]quinoxaline (DiMeIQx)) is one of the more abundant heterocyclic aro matic amines, accounting for similar to 20% of the mutagenic material found in cooked meat. DiMeIQx is metabolically activated, by hepatic m icrosomes from PCB treated rats, to two major and three minor metaboli tes. One major and one minor metabolite were identified as 2-hydroxyam ino-3,4,8-trimethyl-3H-imidazo[4,5-f] quinoxaline and 4,8-trimethyl-2n itro-3H-imidazo[4,5-f]quinoxaline, respectively, confirmed by comparis on of HPLC retention times, and UV and mass spectra of synthetic stand ards. Both metabolites were mutagenic in Salmonella typhimurium TA98 w ithout metabolic activation. The other major metabolite was identified as -amino-8-hydroxymethyl-3,4-dimethyl-3H-quinoxaline by mass and NMR spectral analysis. The two remaining minor metabolites were identifie d as the 2-hydroxyamino- and 2-nitro- derivatives of -8-hydroxymethyl- 3,4-dimethyl-3H-imidazo[4,5-f]qui by UV and mass spectral analysis. Bo th of these metabolites were mutagenic in S.typhimurium TA98 without m etabolic activation.