The research proposed in this grant is directed toward the use of both radioprotective and radiosensitizing drugs in radiation therapy. Protective drugs include WR-2721, and newer more effective drugs of this type, while sensitizing drugs, in the present context, includes both nitroimidazoles and certain alkylating agents. To exploit the combinations of these agents we are proposing to (1) determine optimum timing between the injection of the nitroimidazole and the WR-2721 so that tumor sensitization is maximum while toxicity and pharmacologic interactions are minimized; (2) determine the relationship between the rate of WR-2721 infusion and toxicity or radioprotection, such that our clinical efforts can be optimized; (3) to investigate the biochemical nature of the membrane restriction which limits the absorption of hydrophilic drugs, such as WR-2721; and (4) to identify agents which are quantitatively and/or qualitatively superior to WR-2721 in cancer therapy.