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.
Casciano
D A
DA
Division of Genetic Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
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