2-Acetylaminofluorene (AAF) is a procarcinogen and its activation mechanisms have been investigated in detail. AAF was metabolized to 2-acetylamino-9-fluorenone (AAF=O) and 2-acetylamino-9-fluorenol by S9 mix. The mutagenicity of AAF=O in the presence of S9 mix was equal in potency to that of AAF in
Salmonella typhimurium TA1538, but the activation mechanism of AAF=O was poorly reported. In this study, we investigated possible ultimate species derived from AAF=O;
N-hydroxy-2-acetylamino-9-fluorenone (
N-OH-AAF=O),
N-acetoxy-2-acetylamino-9-fluorenone (
N-OAc-AAF=O),
N-hydroxy-2-amino-9-fluorenone (
N-OH-AF=O), and
N-acetoxy-2-trifluoroacetylamino-9-fluorenone (
N-OAc-TFAAF=O), a model compound for
N-acetoxy-2-amino-9-fluorenone (
N-OAc-AF=O), were synthesized and their mutagenicity was examined in
S. typhimurium TA1538. The activation mechanism in
S. typhimurium TA1538 was also investigated. The compounds in order of decreasing mutagenicity are
N-OAc-TFAAF=O>
N-OH-AF=O>
N-OAc-AAF=O>
N-OH-AAF=O. AAF=O is at least partially responsible for the mutagenicity of AAF, since a small amount of AAF is oxidized to AAF=O in the presence of S9 mix. Furthermore we suggest that an ultimate active species of AAF=O in
S. typhimurium is
N-OAc-AF=O, with the same activation manner as AAF.
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