Metabolic activation in isolated rat hepatocytes.
Hepatocytes were exposed in vitro to the hepatocarcinogen N-hydroxy-2-aminofluorene (N-OH-AAF) in order to determine the nature and repair of DNA adducts formed. N-OH-AAF formed 3 DNA adducts, N-(deoxyguanosin-8yl)-2-acetylaminofluorene (dG-C8-AAF), N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF), and 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene (dG-N2-AAF). The removal of these adducts was measured up to 38 h following cessation of exposure to N-OH-AAF. The dG-C8-AAF adduct was removed with a half-life of about 10 h, while the other two remained relatively constant throughout the incubation period. The dG-C8-AAF adduct is probably responsible for the induction of unscheduled DNA synthesis (UDS) in this model in vitro system.
Division of Genetic Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
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Casciano
D015073:2-Acetylaminofluorene / Q000494:pharmacology / Q000031:analogs & derivatives; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D005449:Fluorenes / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats
D005449:Fluorenes; C018776:N-(deoxyguanosin-8-yl)acetylaminofluorene; C001368:N-hydroxy-2-aminofluorene; D004247:DNA; D015073:2-Acetylaminofluorene; D003849:Deoxyguanosine