Oxygen-dependent free radicals in spermine oxidation cytostatis and chemiluminescence and the role of superoxide dismutase.
Spermine interacted with serum polyamine oxidase (PAO) to arrest proliferation of cultured Bri8 lymphocytes. Arrest was independent of catalase activity and was not directly due to an H(2)O(2) byproduct. Arrest was averted by 3-hydroxybenzyloxyamine, which inactivates the pyridoxal co-factor of PAO. The oxidation of spermine in the presence of different concentrations of PAO was non-linear, which implied complex intermediate events for conversion of spermine to labile di-oxidized spermine (N,N'-bis(3-propionaldehyde)-1,4-butanediamine) with, perhaps, overall generation of free radicals (O(2) (-·) and ·OH) which are damaging to cells. Exogenous free radicals were apparently neither direct participants in cytostasis, nor in the chemiluminescence demonstrable for spermine oxidation. Thiourea, an ·OH scavenger, protected against both proliferation arrest and luminescence. Many other powerful ·OH scavengers, however, were ineffective. Though reaction mixtures reduced ferricytochrome c initially, reduction was not inhibited by superoxide dismutase (SOD) which indicated that the anion O(2) (-·) had not been generated. The powerful reducing capability of di-oxidized spermine itself could have competed against any O(2) (-·) for ferricytochrome c reduction. Nevertheless, O(2) (-·) was generated during further PAO conversion and/or auto-oxidation of di-oxidized spermine. Curiously, addition of SOD to destroy presumptive O(2) (-·) variably potentiated cytotoxicity. Blockage of any anion channels in the cell plasma membrane by stilbene derivatives did not influence cytotoxicity. Thus, findings support our previous evidence that cationic di-oxidized spermine is a potent G(1) inhibitor of cell proliferation. The possibility of intracellular free-radical and thiol involvement is discussed.
D002374:Catalase / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D005609:Free Radicals; D006801:Humans; D008163:Luminescent Measurements; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D010084:Oxidation-Reduction; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000097:blood / Q000494:pharmacology; D013096:Spermine / Q000378:metabolism* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology / Q000502:physiology*
D005609:Free Radicals; D013096:Spermine; D002374:Catalase; D013482:Superoxide Dismutase; D000587:Oxidoreductases Acting on CH-NH Group Donors