FORMATION AND PERSISTENCE OF DNA-ADDUCTS OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE IN THE RAT AND NONHUMAN-PRIMATES

The formation and persistence of the two principal DNA adducts of the food derived carcinogen 1-amino-3-methylimidazo[4,5-f]quinoline (IQ) h ave been investigated in rats and nonhuman primates. DNA adduct format ion in the liver of male Fischer-344 rats occurred in a dose-dependent manner (0.01-20 mg/kg) where osin-8-yl)-2-amino-3-methylimidazo[4,5-f ]quinoline (dG-C8-IQ) and 5-(deoxyguanosin-N-2-yl)-2-amino-3-methylimi dazo (dG-N-2-IQ) accounted for approximately 60-80% and 20-40%, respec tively, of the total adducts observed by P-32 postlabeling. Similar DN A adduct profiles were observed in kidney and colorectal tissue of rat s given a single oral dose of IQ (20 mg/kg) which, when given chronica lly to this species, results in tumorigenesis in liver and colorectum, but not in kidney. dG-C8-IQ was removed more rapidly than dG-N-2-IQ f rom liver and kidney, but removal of both adducts from the colorectum closely followed cell replication. Similar DNA adduct profiles were ob served in liver and extrahepatic tissues of nonhuman primates followin g a single dose of IQ (20 mg/kg). In chronically treated monkeys under going carcinogen bioassay, there was a sharp increase in the contribut ion of dG-N-2-IQ to total DNA adducts in all slowly dividing tissues. There was no preferential accumulation of dG-N-2-IQ in the colon, a ti ssue with a high rate of cell division, and dG-C8-IQ remained the pred ominant lesion. These findings point to a preferential removal of the dG-C8-IQ adduct by enzyme repair system(s) in slowly dividing tissues in both rats and nonhuman primates.