To examine the possible role of reactive oxygen metabolites in lymphocyte-mediated cytolysis, the morphology of cell death following the exposure of cells to reactive oxygen metabolites in vitro was compared with the morphology of cell-mediated killing in vitro of tumour cells by natural killer (NK) cells. Ultrastructural examination of human tumour cells that were dying following incubation for 60 min with the oxygen metabolite generating systems, xanthine-xanthine oxidase or t-butylhydroperoxide, showed that cell death in both instances was exclusively by necrosis. It was unclear which oxygen metabolites were involved in killing. Cell death was not decreased by the addition of superoxide dismutase, a scavenger of the superoxide anion, to the xanthine-xanthine oxidase mixture. Although the cells were not killed by incubation with 1 mM-hydrogen peroxide, the addition of catalase, a scavenger of hydrogen peroxide, to the xanthine-xanthine oxidase mixture significantly reduced cell death. The addition of scavengers for the hydroxyl radical to either the xanthine-xanthine oxidase mixture or t-butylhydroperoxide gave inconsistent protection. In contrast, tumour cell killing mediated by natural killer cells was by apoptosis, a morphologically distinct mode of cell death with a different basic mechanism, indicating that reactive oxygen metabolites are not directly involved in lymphocyte-mediated cytolysis.

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