POTENTIAL CHEMOPREVENTIVE AGENTS

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The objective of this study is to employ the Azoxymethane induced rat colon tumor model to screen for potential chemopreventive agents. This model induces adenomas and carcinomas in the colons of treated F344 male rats. The resulting tumors appear histologically similar to human tumors and furthermore exhibit Ki Ras mutations in approximately 50% of tumors similarly to humans. We will examine three individual agents for their chemopreventive activity (Cox 2 inhibitor, retinoid, ODC inhibitor) as well as combinations of agents NSAIDS or ODC inhibitor plus retinoids. The latter studies are based on our recent findings that some of the retinoids appear to be effective agents in the AOM tumor model. Should any of these agents or combinations of agents prove efficaceous in this model they will be advanced for further preclinical biological and toxicologic studies prior to their development in the clinic.