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Side effects of non steroidal anti-inflammatory drugs (NSAID), like Sulindac (SU) hamper their use for chemoprevention in familial adenomatous polyposis (FAP) and sporadic colorectal cancer (CRC) patients, at high risk. Mutations in APC, causing FAP and present in CRC, confer resistance to apoptosis. NSAID, as well as natural compounds like curcumin (CU) or 3,3’-Diindolylmethane (DIM), endowed of chemopreventive activity, increase apoptosis with various mechanisms. Recently, PIRC rat (polyposys in rat colon) mutated in Apc, has been described as a genetic model of FAP. Aiming at finding an effective chemopreventive strategy with minimal side effects we propose a combination of low doses of SU, together with DIM and CU to prevent carcinogenesis in PIRC. This combination will be also tested in 1,2-dimethylhydrazine-induced colon carcinogenesis in rats, a model of sporadic CRC. Mechanisms of action and characterization of PIRC rats will be also carried out
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