Metabolic activation in isolated rat hepatocytes.

Abstract

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.