Cytotoxicity of nitric oxide in Fu5 rat hepatoma cells: evidence for co-operative action with hydrogen peroxide.
The NO-releasing compounds 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1), sodium nitroprusside (SNP) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) mediated a rapid loss of viability of Fu5 rat hepatoma cells. SIN-1 in addition to NO also released the superoxide anion radical (O2-.). Its cytotoxicity, however, was not affected by superoxide dismutase. In contrast, the H2O2-converting enzyme catalase significantly, but not completely, diminished cell damage, indicating participation of H2O2 in the tumoricidal activity of SIN-1. Glucose oxidase (5 m-units/ml), producing similar amounts of H2O2 to 5 mM SIN-1, had no effect on cell viability. When 5 m-units/ml glucose oxidase was added to incubations with 5 mM SNP, which alone initiated cell injury of about 40%, cell damage was significantly increased up to 95%. Similar results were observed with 1 mM SNAP and 20 m-units/ml xanthine oxidase, which mediated cytotoxicity of about 90% when both compounds were added together, compared with 35% and 55% cell injury, respectively, induced by the single compounds. The results indicate that a co-operative action with H2O2 enhances the tumoricidal activity of NO in Fu5 cells. No evidence for an interplay of NO with O2-. in cytotoxicity, e.g. via the peroxynitrite anion (ONOO-), was found.
Ioannidis
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Institut für Physiologische Chemie, Universitätsklinikum, Essen, Federal Republic of Germany.
de Groot
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D000818:Animals; D006528:Carcinoma, Hepatocellular; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D005949:Glucose Oxidase / Q000378:metabolism / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008113:Liver Neoplasms; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000633:toxicity; D009569:Nitric Oxide / Q000633:toxicity*; D009599:Nitroprusside / Q000633:toxicity*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000633:toxicity; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000633:toxicity*; D014969:Xanthine Oxidase / Q000378:metabolism / Q000494:pharmacology
D014665:Vasodilator Agents; D013481:Superoxides; D009599:Nitroprusside; D009569:Nitric Oxide; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; D006861:Hydrogen Peroxide; D008981:Molsidomine; D005949:Glucose Oxidase; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010396:Penicillamine