SIMILAR PATTERNS OF DNA ADDUCT FORMATION OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE IN THE FISCHER-344 RAT, CDF1 MOUSE, CYNOMOLGUS MONKEY AND SALMONELLA-TYPHIMURIUM

2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is a known liver carcinogen in the Fischer 344 rat, the CDF1 mouse and in the cynomolgus monkey. Using P-32-postlabeling assays, we compared IQ-DNA adduct formation in the liver of IQ-treated Fischer 344 rats, CDF1 mice and cynomolgus monkeys with that in Salmonella typhimurium (strain TA98) incubated with IQ (in the presence of a liver S9 activating system) or N-hydroxy-IQ, and with that in calf thymus DNA reacted with IQ (in the presence of a liver S9 activating system) or N-hydroxy-IQ. Up to five adducts could be detected, the pattern of which was identical in all cases. The major adduct co-chromatographed with standard N-(deoxyguanosin-8-yl)-IQ in all cases and comprised 54.7-82.8% of the total. The four minor adducts were not identified. It is concluded that N-(deoxyguanosin-8-yl)-IQ is the major IQ-DNA adduct under all experimental conditions and that the pattern of N-hydroxy-IQ-DNA adducts is identical to that found in the liver of animals exposed to IQ, and to that found after reacting IQ with DNA in the presence of a liver S9 activating system. Thus, N-hydroxylation of IQ is a critical step in the formation of IQ-DNA adducts.