METABOLISM AND ACTIVATION OF 2-ACETYLAMINOFLUORENE IN ISOLATED RAT HEPATOCYTES

  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (8) , 3268-3275
Abstract
The metabolism of [the precarcinogen] 2-acetylaminofluorene (AAF) and the activation of AAF to covalently bound and mutagenic [tested against Salmonella typhimurium TA 98] intermediates were studied in isolated rat hepatocytes. The cell system readily formed oxidized, deacetylated and conjugated AAF metabolites. Pretreatments of animals with the inducer .beta.-naphthoflavone led to increases in phenolic, conjugated and covalently protein-bound products. Addition of 4-nitrophenol, a substrate for conjugation, increased the levels of free phenols and inhibited the formation of water-soluble metabolites. At the same time, the rates of covalent protein binding were decreased. Formation of 9-hydroxy-2-acetylaminofluorene could also be demonstrated. The pathway leading to this alicyclic hydroxylated AAF metabolite was not induced by prior .beta.-naphthoflavone treatment, nor was it inhibited by 4-nitrophenol addition. The cell system converted AAF and aminofluorene and 2,4-diaminoanisole to mutagenic intermediates which were released into the incubation medium. 2-Aminofluorene was considerably more mutagenic than was AAF in this system. Addition of microsomes increased the mutagenicity of AAF, but not that of 2-aminofluoreene or 2,4-diaminoanisole, presumably by deacetylation of N-hydroxy-2-acetylaminofluorene to N-hydroxy-2-aminofluorene.