EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS IN ANIMAL MOD

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The objectives of the proposed studies will be to investigate a series of four compounds for chemopreventive activity in the 4NQO model. The MTDs of at least two of the four agents to be examined (iNOS inhibitor, antiangiogenic agent, Cox-2 inhibitor, TBA) are known. Therefore preliminary toxicity studies are being performed on only two agents. Five week old male F344 rats are scheduled for administration 20 ppm 4NQO in the drinking water ad libitum. Rats are being maintained continually on 4NQO containing water for a period of 10 weeks. At the end of this time period rats regular water is given. Starting 2 days following the cessation of 4NQO rats are being given chemopreventive agents for an additional 22 weeks. At the end of this time period rats are being sacrificed by CO2 asphyxiation. All rats are sacrificed 32 weeks following the initiation of treatment with 4NQO. At necropsy various other tissues, particularly of the oral cavity, are being examined grossly. Tongues of rats are fixed in formalin. Other tissues of the oral cavity are fixed in formalin. For histopathologic confirmation, tissues and gross lesions shall be fixed in 10% buffered formalin, embedded in paraffin blocks and processed by conventional histologic methods using H&E staining.