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 32P-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. 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.
Schut
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HA
Department of Pathology, Medical College of Ohio, Toledo 43614.
Snyderwine
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EG
Zu
H X
HX
Thorgeirsson
S S
SS
D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D004249:DNA Damage; D008099:Liver / Q000187:drug effects; D008252:Macaca fascicularis; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens; D011804:Quinolines / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012486:Salmonella typhimurium / Q000187:drug effects*
D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline