Oxidative transformation of 2-acetylaminofluorene by a chemical model for cytochrome P450: A water-insoluble porphyrin and tert-butyl hydroperoxide Original Research Article

Oxidation of 2-acetylaminofluorene (AAF), a carcinogen, by a chemical model for cytochrome P450 was investigated to identify an active mutagen and elucidate the oxidation pathway. The oxidation system consisted of a water-insoluble tetrakis(pentafluorophenyl)porphyrinatoiron(III) chloride and tert-butyl hydroperoxide. The mutagen derived from AAF by the chemical model was 2-nitro-9-fluorenone (NO2Fdouble bond; length as m-dashO), which was mutagenic in Salmonella typhimurium TA1538. AAF was oxidized initially at position 9 of the fluorene carbon by the chemical model forming 2-acetylamino-9-fluorenol (AAF–OH), and then oxidized further to 2-acetylamino-9-fluorenone (AAFdouble bond; length as m-dashO) as a major product. Initial oxidation of the nitrogen formed 2-nitrofluorene (NO2F), and further oxidation yielded 2-nitro-9-fluorenol (NO2F–OH) as a minor product. These products, AAF–OH, AAFdouble bond; length as m-dashO, NO2F, and NO2F–OH, and their presumable common intermediate, N-hydroxy-2-acetylaminofluorene, were oxidized by the chemical model, and the formation of NO2Fdouble bond; length as m-dashO was determined. These results showed that NO2Fdouble bond; length as m-dashO was the mutagen derived from AAF in the presence of the chemical model and was formed via oxidation of N-OH–AAF, NO2F, and NO2F–OH. These results may lead to a new metabolic pathway of AAF.