Nitroxides as radiation protectors

Abstract

Selective protection of normal tissues from the damaging effects of ionizing radiation is an important objective in cancer treatment research. Likewise, radioprotective agents may be useful in protecting the human population in the event of radiation-related accidents or military conflicts. Over the past decade, we have identified stable nitroxide compounds as a unique class of antioxidants with demonstrated radioprotective properties. We have shown that nitroxides at nontoxic concentrations are effective as in vitro and in vivo antioxidants when oxidation is induced by superoxide, hydrogen peroxide, organic hydroperoxides, ionizing radiation, or specific DNA damaging anticancer agents. Studies have shown that nitroxides protect against radiation-induced DNA damage, chromosome aberrations, mutation induction, cell killing, and lethality in mice that receive whole-body irradiation. Whether these agents provide radioprotection for low-level radiation doses remains to be determined.