EFFICACY OF CHEMOPREVENTIVE AGENTS IN ANIMAL MODELS

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This study examines the effects of chemopreventives primarily on tumor endpoints and a more limited number of potential surrogate endpoint biomarkers for their modulation by these agents. Endpoints include: A) Various cell cycle regulated proteins i.e. cyclins and their related kinases. e.g. Cyclin D1 B) Measures of DNA synthesis(BudR or PCNA); C) Telomerase . These endpoints lend themselves to quantitative analysis. These markers are altered in a variety of epithelial cancers. Therefore working out various parameters related to these endpoints in this specific model should prove applicable for a wide variety of tumors. One further objective of these studies is to employ agents beginning up to 10 weeks following the beginning of the administration of UV to the mice. The objectives of this study are: 1) To employ the SKH hairless mouse model to examine three agents starting chemopreventive treatment either immediately prior to following or 10 weeks following treatment with the agents. These agents Indomethacin, DFMO and a compound to be named later will all be administered in feed and 2) To employ two effective agent and to determine whether they can modulate expression of potential biomarkers (e.g. cell cycle proteins (e.g. PCNA),cyclin levels and telomerase activity).