Polyunsaturated fatty acids stimulate superoxide formation in tumor cells: A mechanism for specific cytotoxicity and a model for tumor necrosis factor?

Some neoplastic cell lines are readily killed when incubated in the presence of polyunsaturated fatty acids (PUFA). In an attempt to elucidate this phenomenon, we studied PUFA-driven superoxide (O2^-) production by cultured NS-1 cells (murine lymphoid tumor cells). We find: (1) Even in the absence of added PUFA, NS-1 cells generate O2^- (i.e., reduce nitroblue tetrazolium). (2) addition of PUFA increases O2^- by >50%. (3) Artificial loading of NS-1 cells with liposome encapsulated superoxide dismutase prevents the majority of spontaneous and PUFA-driven NBT reduction. We conclude that PUFA drives O2^- generation by tumor cells, that this generation is largely intracellular, and that this phenomenon may help explain toxicity of PUFA for tumor cells.