Thiols have long been studies as radioprotective compounds, yet the mechanism of protection is still poorly understood. We have developed means by which the major cellular thiol, glutathione, can be either depleted or elevated and the access radiosensitivity. We have shown that glutathione is not a major protector from the effects of ionizing radiation in mitotically active cells. Work is underway to synthesize compounds varying in chemical structure that may provide insight into the mechanism and requirements of radioprotection agents. The importance of membrane in specialized tissue such as lymphocytes is being studied. The relationship of membrane oxidation and protection from such oxidative damage is being studied. The importance of separate thiol dependent detoxification enzymes versus general oxidative detoxification is being studied. Additionally, by evaluation of previously synthesized radioprotectors using structure/activity relation calculations, we plan to evaluate already synthesized and tested compounds as a means to guide the synthesis of new compounds that may afford differential protection to normal versus tumor tissue.
