Interaction of C-nitroso aromatics with polyunsaturated fatty acids: route to lipid peroxidation.

The possibility that the interaction of C-nitroso aromatics with polyunsaturated fatty acids (PUFA) causes lipid peroxidation was investigated through determination of conjugated diene and malodialdehyde (MDA) formation after anaerobic/aerobic vs. aerobic incubations of nitrosobenzene (NOB) or 2-nitrosofluorene (2-NOF) with linoleic, linolenic or arachidonic acid or methyl linolenate. Anaerobic incubation of NOB or 2-NOF with linolenic acid at the molar ratio of 1:1 for 24 h yielded approximately 5.5-13% of the PUFA as conjugated diene which appeared stable upon exposure to air. Interaction of PUFA and 2-NOF or NOB yielded MDA, the amounts of which were significantly greater when 24-h anaerobic preceded 1-6-h aerobic incubation. Furthermore, the differences in the amounts of MDA resulting from 24- and 0-h anaerobic incubations were significantly greater when the molar ratio of 2-NOF (or NOB) to PUFA was increased (2.0 greater than 1.0 greater than 0.5). Superoxide dismutase or catalase had no effect on the yields of MDA following either anaerobic/aerobic or aerobic incubations of PUFA and 2-NOF. EDTA (1 or 10 microM) had no effect on the yields of MDA from aerobic incubations, but it decreased the amounts of MDA (by approximately 30 or 60%, respectively) from anaerobic/aerobic incubations. The data suggested that inhibition by EDTA was due to chelation of trace iron, which following anaerobic interaction of PUFA and 2-NOF might have been reduced to Fe2+ and contributed to the enhanced lipid peroxidation. Thus, adduction of C-nitroso aromatics to PUFA yields radical species which directly and/or via reaction with trace iron lead to lipid peroxidation. The lipophilicity of C-nitroso aromatics suggests that this process may be of consequence in their mutagenesis/carcinogenesis.