Abstract

The carcinogen 2-acetylaminofluorene undergoes metabolic activation to 2-nitrosofluorene (NOF). NOF is a powerful mutagen in the Ames assay conducted with TA 98 strain of <i>Salmonella typhimurium</i> in the absence of microsomal activation system. We have shown that NOF adds to unsaturated lipids in microsomes and liposomes to yield free radicals. NOF adds to methyl oleate or 2,3-dimethylbut-2-ene in an Alder-ene fashion to form a hydroxylamine derivative which undergoes oxidation to yield a fairly stable nitroxyl free radical. The second derivative electron spin resonance spectrum of the NOF-methyl oleate adduct is a triplet of a quartet with a 1:3:3:1 intensity pattern. This suggests that the free electron interacts with one nitrogen (a<sub>N</sub> = 11.5 G) and three approximately equivalent protons (a<sup>1</sup><sub>H</sub> ≃ a<sup>2</sup><sub>H</sub> ≃ a<sup>3</sup><sub>H</sub> ≃ = 3.5 G). The second derivative spectrum of the NOF-2,3-dimethylbut-2-ene adduct is more complex involving a triplet of 14 lines each. Both adducts were less mutagenic than NOF in the Ames assay. Membrane alterations due to NOF-lipid adduct formation may be a factor in 2-acetylaminofluorene-induced carcinogenesis.

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