The long range goal of the proposed research is to develop a new class of chemical radiosensitizers. In order to achieve our overall objective, our plan will be to: a. Synthesize potential radiosensitizers from a class that does not contain a nitro group, specifically isoindole quinones; b. determine physicochemical properties of these compounds; c. determine the radiation chemical characteristics of these quinone derivatives; d. determine the toxicity and cytotoxicity of these compounds using in vivo and in vitro systems; e. determine the radiosensitization potentialities of the isoindole quinones in an in vivo system using EHS sarcoma and KHT sarcoma transplanted in mice; f. investigate the mechanism of action of these compounds using different combined modalities in the radiation and chemical therapeutic treatment of cancerous tissues. It is hoped that these investigations will provide a basis for the development of a new class of chemical radiosensitizers, which may lack the undesired side effects encountered with some of the currently tested sensitizers.
