Mutagenic metabolites in urine and feces of rats fed with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, a carcinogenic mutagen present in cooked meat.

To study the in vivo fate of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), a carcinogenic mutagen present in cooked meat, rats were fed MeIQx in the diet and their urine and feces were analyzed for the metabolites. The isolation procedure included specific adsorption of MeIQx derivatives to blue cotton and subsequent fractionations by thin layer chromatography on silica gel and by high pressure liquid chromatography. Attention was focused on mutagenically active metabolites. Three metabolites were isolated from the urine, and their structures were elucidated on the basis of 1H nuclear magnetic resonance, ultraviolet, and mass spectra. The first metabolite characterized was 2-amino-8-hydroxymethyl-3-methylimidazo[4,5-f]quinoxaline (Compound I), the second was 2-acetylamino-3,8-dimethylimidazo[4,5-f]quinoxaline (Compound II), and the third was 2-amino-8-methylimidazo[4,5-f]quinoxaline (Compound III). Compound I was isolated also from the feces. Compounds I-III were mutagenic to Salmonella typhimurium TA98 with metabolic activation. The mutagenic potency of Compounds I and II was as high as that of MeIQx, and that of Compound III was much lower than that of MeIQx.