CHEMOPREVENTION OF CARCINOGENESIS BY NUCLEOPHILES

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The objective of this proposal is to obtain compounds that will trap direct-acting carcinogens within the lumen of the gastrointestinal tract and prevent them from attacking host tissues. Two major attributes required of the compounds are efficacy as trapping agents and retention within the gastrointestinal tract. This latter attribute is important in providing effective concentrations throughout the entire alimentary tract and potentially providing safe compounds in terms of lack of toxicity. The specific aims of the proposal are as follows: 1. To identify candidate compounds and provide these for testing. 2. To determine the capacity of the candidate compounds to react with a diverse group of direct-acting carcinogens in vitro and also with fecapentaene. 3. To determine retention of the test compounds within the gastrointestinal tract. 4. To determine the capacity of test compounds to trap direct-acting carcinogens within the lumen of the gastrointestinal tract in vivo. 5. To determine the capacity of test compounds to inhibit carcinogen-induced neoplasia resulting from administration of direct-acting carcinogens. 6. To determine toxicity of effective test compounds. THE COLLABORATIVE PROJECT consists of an administrative unit and laboratories at two institutions. One of these is the University of Minnesota - Department of Laboratory Medicine and Pathology and Department of Chemistry. The other is the Illinois Institute of Technology.