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Intravascular death of disseminated cancer cells mediated by superoxide anion.

The release of radiolabelled Lewis lung carcinoma cells arrested in the vasculature of the major organs of mice after intravenous injection was significantly inhibited in animals treated with the oxygen radical scavenger, superoxide dismutase. There was a parallel increase in the numbers of tumor nodules which developed after injection of non-radiolabelled cells into superoxide dismutase-treated mice. The results indicate that superoxide anion plays an important role in the lethal release of arrested cancer cells, either directly since the radical is cytotoxic or possibly indirectly since its metabolites are also highly toxic. It is suggested that a major source of toxic oxygen species is the polymorphonuclear leukocyte.