PT - JOURNAL ARTICLE AU - Karen H. Dingley AU - Stewart P. H. T. Freeman AU - David O. Nelson AU - R. Colin Garner AU - Kenneth W. Turteltaub TI - Covalent Binding of 2-Amino-3,8-dimethylimidazo[4,5-<em>f</em>]quinoxaline to Albumin and Hemoglobin at Environmentally Relevant Doses DP - 1998 Aug 01 TA - Drug Metabolism and Disposition PG - 825--828 VI - 26 IP - 8 4099 - http://dmd.aspetjournals.org/content/26/8/825.short 4100 - http://dmd.aspetjournals.org/content/26/8/825.full SO - Drug Metab Dispos1998 Aug 01; 26 AB - Covalent binding of the food-borne heterocyclic amine 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) to albumin and hemoglobin (Hb), 3.5–6.0 hr after oral administration of a single dose of either 21.3 or 228.0 μg of [14C]MeIQx (304 and 3257 ng/kg of body weight, respectively, based on a 70-kg subject weight), was studied in human volunteers using accelerator mass spectrometry. Human protein adduct levels were compared with data obtained for male F344 rats 4.5 hr after oral administration of 0.94–11,420 ng/kg of body weight [14C]MeIQx. Dose-dependent levels of MeIQx-albumin and MeIQx-Hb adducts were detected in both humans and rats. In each case, the regression coefficient (slope) of the dose-response curve was approximately 1. The highest levels of adduct formation per unit dose of MeIQx occurred with human albumin, followed by rat albumin, human Hb, and rat Hb (in that order). Although the human subjects were elderly and underwent colon resection surgery during the study period, the results indicate that formation of albumin and Hb adducts is dose dependent and that a trend exists for higher adduct levels per unit dose in humans, compared with F344 rats. Furthermore, MeIQx-albumin adducts are likely to provide a more sensitive marker of exposure to MeIQx than are MeIQx-Hb adducts. The American Society for Pharmacology and Experimental Therapeutics