Thiols have long been studied 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 then access radiosensitivity. We have shown that glutathione is not a major protector for x-ray. Plans are to synthesize compounds varying in chemical structure that may provide radioprotection. The importance of membrane in specialized tissue such as lymphocytes is being studied. The importance of separate thiol dependent detoxification enzymes versus general oxidative detoxification is being studied. Additionally, by elevation of previously synthesized radioprotectors using structure/activity relation calculations, we plan to synthesize new compounds that may afford differential protection to normal vs tumor tissue.
