COVALENT BINDING OF 2-AMINO-3,8-DIMETHYLIMIDAZO[4,5-F]QUINOXALINE TO ALBUMIN AND HEMOGLOBIN AT ENVIRONMENTALLY RELEVANT DOSES - COMPARISON OF HUMAN-SUBJECTS AND F344 RATS

Covalent binding of the food-borne heterocyclic amine 2-amino-3,8-dime thylimidazo[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 o r 228.0 mu g of [C-14]MeIQx (304 and 3257 ng/kg of body weight, respec tively, based on a 70-kg subject weight), was studied in human volunte ers using accelerator mass spectrometry. Human protein adduct levels w ere compared with data obtained for male F344 rats 4.5 hr after oral a dministration of 0.94-11,420 ng/kg of body weight [C-14]MeIQx. Dose-de pendent 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). Althoug h the human subjects were elderly and underwent colon resection surger y during the study period, the results indicate that formation of albu min and Hb adducts is dose dependent and that a trend exists for highe r adduct levels per unit dose in humans, compared with F344 rats. Furt hermore, MeIQx-albumin adducts are likely to provide a more sensitive marker of exposure to MeIQx than are MeIQx-Hb adducts.