Inability of polyethylene-glycol substituted copper- and zinc-containing superoxide dismutase to protect mice against radiation lethality.

The superoxide radical has been implicated in the mediation of radiation damage and CuZn superoxide dismutase, given to mice immediately before or after irradiation has, in several studies, reduced radiation lethality. CuZn superoxide dismutase has a very short plasma half-life, but if the enzyme is substituted with polyethylene-glycol a markedly increased circulation time can be achieved. In the present study an 80-fold increase in plasma superoxide dismutase activity was brought about in CBA mice by intraperitoneal injection of 7.5 ml polyethylene-glycol substituted CuZn superoxide dismutase. Although the treatment was found to have a slight radioprotective effect with a dose-modifying factor of 1.02 (p = 0.027), CuZn superoxide dismutase inactivated by hydrogen peroxide-treatment was found to be equally protective. The radioprotective effect of polyethylene-glycol substituted CuZn superoxide dismutase therefore does not seem to be dependent on the enzyme activity.