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.
R. Sridhar, M. J. Hampton, J. E. Steward, and R. A. Floyd, "Studies on the Mutagenicity and Electron Spin Resonance Spectra of Nitrosofluorene-Lipid Adducts," Appl. Spectrosc. 34, 289-293 (1980)