Comparison of DNA-adduct and tissue-available dose levels of MeIQx in human and rodent colon following administration of a very low dose

[2-C-14]2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) was administe red orally (304 ng/kg body-weight dose based upon an average 70-kg-body-wei ght subject) to 5 human colon-cancer patients (58 to 84 years old), as well as to F344 rats and B6C3F1 mice. Colon tissue was collected from the human subjects at surgery and from the rodents 3.5 to 6 hr after administration. Colon DNA-adduct levels and tissue available doses were measured by accele rator mass spectrometry (AMS), The mean levels of MelQx in the histological ly normal colon tissue were not different among the human (97 +/- 26 pg Mel Qx/g), rat(133 +/- 15 pg/g) or mouse (78 +/- IO pg/g) tissues; and no diffe rence existed between the levels detected in human normal and tumor tissue (101 +/- 15 pg/g), Mean DNA-adduct levels in normal human colon (26 +/- 4 a dducts/10(12) nucleotides) were significantly greater(p < 0.01) than in rat s (17.1 +/- 1 adduct/10(12) nucleotides) or mice (20.6 +/- 0.9 adduct/10(12 ) nucleotides). No difference existed in adduct levels between normal and t umor tissue in humans. These results show that MelQx forms DNA adducts in h uman colon at low dose, and that the human colon may be more sensitive to t he effects of MelQx than that of mice or rats. (C) 1999 Wiley-Liss, Inc.