title: Polyunsaturated fatty acids stimulate superoxide formation in tumor cells: a mechanism for specific cytotoxicity and a model for tumor necrosis factor?
abstract: 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 greater than 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.
authors.affiliation: Research Laboratories, V. A. Medical Center, Minneapolis, Minnesota 55417.
authors.forename: D A
authors.initials: DA
authors.lastname: Peterson
authors.forename: N
authors.initials: N
authors.lastname: Mehta
authors.forename: J
authors.initials: J
authors.lastname: Butterfield
authors.forename: M
authors.initials: M
authors.lastname: Husak
authors.forename: M M
authors.initials: MM
authors.lastname: Christopher
authors.forename: S
authors.initials: S
authors.lastname: Jagarlapudi
authors.forename: J W
authors.initials: JW
authors.lastname: Eaton
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D008081:Liposomes; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000378:metabolism; D013481:Superoxides / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D005231:Fatty Acids, Unsaturated; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D013482:Superoxide Dismutase