title: 2-Nitrosofluorene and N-hydroxy-2-aminofluorene react with the ubiquinone-reduction center (center N) of the mitochondrial cytochrome bc1 complex.
abstract: We determined the sites of artificial electron transfer onto 2-nitrosofluorene (NOF), a metabolite of carcinogenic 2- acetylaminofluorene in mitochondria and isolated cytochrome bc1 complex. NOF-induced O2 consumption in mitochondria was sensitive to antimycin A, but insensitive to myxothiazol. In the isolated cytochrome bc1 complex, NOF induced rapid MOA-stilbene-insensitive reoxidation of cytochrome b, whereas in the presence of antimycin A, reoxidation was very slow. The corresponding hydroxylamine, N-hydroxy-2-aminofluorene (N-OH-AF), reduced cytochrome b specifically through center N of the cytochrome bc1 complex. We conclude that NOF and N-OH-AF bind to center N of the cytochrome bc1 complex and act as electron acceptor and donor, respectively. The N-OH-AF/NOF interconversion is considered to be involved in the cytotoxicity of 2-acetylaminofluorene in vivo.
authors.affiliation: Institut für Toxikologie, Universität Würzburg, Germany.
authors.forename: P C
authors.initials: PC
authors.lastname: Klöhn
authors.forename: U
authors.initials: U
authors.lastname: Brandt
authors.forename: H G
authors.initials: HG
authors.lastname: Neumann
mesh_terms: D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D003573:Cytochrome b Group / Q000378:metabolism; D004227:Dithionite / Q000494:pharmacology; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005449:Fluorenes / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008689:Methacrylates; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013267:Stilbenes / Q000494:pharmacology; D013772:Tetramethylphenylenediamine / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014451:Ubiquinone / Q000378:metabolism*; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D003573:Cytochrome b Group; D005449:Fluorenes; D008689:Methacrylates; D009603:Nitroso Compounds; D013267:Stilbenes; D013844:Thiazoles; D014475:Uncoupling Agents; C056108:3-methoxy-2-(2-styrylphenyl)propenic acid methyl ester; D014451:Ubiquinone; D004227:Dithionite; C012458:2-nitrosofluorene; C001368:N-hydroxy-2-aminofluorene; D000968:Antimycin A; C030517:myxothiazol; D014450:Electron Transport Complex III; D011190:Potassium Cyanide; D013772:Tetramethylphenylenediamine