Metabolism of the food carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in isolated rat liver cells.

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was transformed to at least 10 metabolites in suspensions of hepatocytes isolated from Aroclor 1254 treated rats. Combining biochemical data such as effects on MeIQx metabolism of metabolic modulators and incorporation of radioisotopic sulfur with UV, mass and 1H-NMR spectroscopy, we elucidated the structures of six metabolites. About 40% of the MeIQx was transformed to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxalin-4(or5)-yl sulfate. Other oxygenated metabolites were 2-amino-8-hydroxymethyl-3-methylimidazo[4,5-f]quinoxalin-4(or 5)-yl sulfate and 2-amino-4(or5)-beta-D-glucuronopyranosyloxy-3,8-dimethyli midazo[4,5-f] quinoxaline. Evidence was obtained that a glutathione conjugate was formed. This metabolite, and the other oxygenated metabolites were probably formed in P-450 catalyzed reactions. Two metabolites, 2-beta-D-glucuronopyranosylamino-3,8-dimethylimidazo[4,5-f]q uinoxaline and the N-(3,8-dimethylimidazo[4,5-f]quinoxaline-2-yl) sulfamate, were direct conjugates of MeIQx.