Requirements of radioprotectors for military and emergency needs

Uncontrolled exposure to radiation from nuclear weapons, space, or accidents presents challenges unlike those met in radiotherapy. For example, the time and quality of exposure are uncertain. Thus it is necessary to develop radioprotectors that can be given chronically (e.g. as vitamin combinations), or shortly before exposure (e.g. as WR-2721 and related compounds), or after exposure (e.g. as immunomodulators) to cover all possible situations of use. Also, for military purposes, performance capability, as well as survival from acute effects, must be maintained. In contrast to clinical and experimental exposure, it is likely that stem cells will survive in military and accident situations, making supportive therapy (e.g. fluids, antibiotics) of real value. Radioprotectors that can increase cell survival or enhance repopulation by the remaining cells can reduce the time required for supportive therapy and enhance its effectiveness. First-generation agents to accomplish this may be combinations of agents to mitigate free radical damage such as dietary supplements or WR-2721 and related compounds. Immunomodulators, either microbial agents (e.g. glucan, TDM) or recombinant cytokines (e.g. interleukin-1, colony-stimulating factor), can enhance hematopoietic and functional cell recovery after irradiation. Synergistic effects can be demonstrated with some combinations of these agents. This is important because agents with individual DRFs of less than two can be significant radioprotectors in combinations. Whether these combinations are effective against combined injury remains to be determined. Future research into mechanisms of radiation-induced damage and natural repair mechanisms should lead to even better second-generation radioprotectants.(ABSTRACT TRUNCATED AT 250 WORDS)