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Over the years, extensive experimental studies of radiation-protective agents have enhanced our knowledge of radiation physics, chemistry, and biology. However, translation of agents from animal testing to use in various scenarios, such as prophylactic adjuncts in radiotherapy or post-exposure treatments for potential victims of radiation accidents/incidents, has been slow. Nevertheless, a number of compounds are now available for use in a variety of radiation situations. These include agents approved by the U.S. Food and Drug Administration for use in reducing exposure to internal radionuclides (Prussian blue, calcium diethylenetriamene pentaacetate (DTPA) and zinc DTPA, potassium iodide) and amifostine for alleviating xerostomia associated with radiotherapy. Consensus groups have also recommended other therapies such as granulocyte colony-stimulating factor for radiation-induced neutropenia. The variety of prophylactic and therapeutic agents in the research pipeline includes those that are naturally-occurring with low toxicity, provide a long window of protection, protect normal tissue while sensitising tumours, or act via receptors and modulate biological processes such as induction of genes responsible for radioresistance. The search for agents that protect against acute and late effects of ionising radiation injury will undoubtedly continue into the future and influence other areas of radiation research.

The role of reactive oxygen species in ionizing radiation injury and the potential of antioxidants to reduce these deleterious effects have been studied in animal models for more than 50 years. This review focuses on the radioprotective efficacy and the toxicity in mice of phosphorothioates such as WR‐2721 and WR‐151327, other thiols, and examples of radioprotective antioxidants from other classes of agents. Naturally occurring antioxidants, such as vitamin E and selenium, are less effective radioprotectors than synthetic thiols but may provide a longer window of protection against lethality and other effects of low dose, low‐dose rate exposures. Many natural antioxidants have antimutagenic properties that need further examination with respect to long‐term radiation effects. Modulation of endogenous antioxidants, such as superoxide dismutase, may be useful in specific radiotherapy protocols. Other drugs, such as nimodipine, propranolol, and methylxanthines, have antioxidant properties in addition to their primary pharmacological activity and may have utility as radioprotectors when administered alone or in combination with phosphorothioates.

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