The binding of N-hydroxy-2-acetylaminofluorene to DNA and repair of the adducts in primary rat hepatocyte cultures.
Primary cultures of rat hepatocytes were exposed to [ring-3H]-N-hydroxy-2-acetylaminofluorene (N-OH-AAF) for 4 h, and the RNA and DNA nucleoside adducts were isolated and identified by h.p.l.c. The DNA adducts were shown to be N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-C8-AAF), N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF), and 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene (dG-N2-AAF), while the RNA adducts were N-(guanosin-8-yl)-2-acetyl-aminofluorene, and N-(guanosin-8-yl)-2-aminofluorene. The removal of these adducts was measured up to 38 h following the cessation of exposure of the hepatocytes to N-OH-AAF. The dG-C8-AAF adduct was removed with a half-life of approximately 10 h, while dG-N2-AAF and dG-C8-AF remained constant for 14 h, followed by a slow rate of removal. The dG-C8-AAF adduct initially composed about 60% of the total DNA adducts of primary hepatocytes in contrast to the 20% found in liver in vivo. The formation of the 3 DNA adducts and the different rates of repair indicate that primary cultured rat hepatocytes may be a valuable system to study initiation of liver carcinogenesis by N-OH-AAF.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D006868:Hydrolysis; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D012313:RNA / Q000378:metabolism; D051381:Rats
D006881:Hydroxyacetylaminofluorene; D012313:RNA; D004247:DNA; D015073:2-Acetylaminofluorene