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

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Abstract
2-Amino-3-methylimidazo [4,5-f]quinoline (IQ) is a known liver carcinogen in the Fischer 344 rat, the CDF1 mouse and inthe cunomolgus monkey. Using 32P-postlabeling assays, we compared IQ-DNA adduct formation in the liver of IQ-treated Fischer 344 rats, CEF1 mice abd 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. Up to five adducts could be detected, the pattern of which was identical in all cases. The major adduct co-chromatographed with standard N-(deoxyguanosine-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-(deoxyguanosine-8-yl)-IQ is the major IQ-DNA adduct under all expermental conditions and that the pattern of N-hydrosy-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.

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