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

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 (NO2FO), 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 (AAFO) 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, AAFO, NO2F, and NO2F–OH, and their presumable common intermediate, N-hydroxy-2-acetylaminofluorene, were oxidized by the chemical model, and the formation of NO2FO was determined. These results showed that NO2FO 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.

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