PRECLINICAL EVALUATION OF INTERMEDIATE ENDPOINTS

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INHIBITION OF UV-INDUCED SKIN CARCINOGENESIS IN SKH HAIRLESS MICE; SCREENING AND RANKING OF CHEMOPREVENTIVE. This project measures the inhibition of UV-induced skin carcinogenesis in SKH hairless mice to screen and rank chemopreventive agents. The studies utilize compute- assisted quantitative image analysis (CIA) to measure a broad range of specialized chromatin texture features. SKH hairless mice, 6-8 weeks of age and weighing 18-22 grams, are being used. The control group is being exposed to a natural 12 hr/dark, 12/hr light cycle of window filtered sunlight. All remaining groups are being exposed to light emitted by spotlights equipped with dichroic diffusers incorporating tungsten halogen quartz lamps. Sentinel groups of 10 mice are being sacrificed at 0, 6, 8, 10, 12, 14, 16, 18 and 20 weeks after start of UV treatment and strips of their dorsal skin examined histologically. Strips of their dorsal skin examined histologically. Strips of dorsal skin are digitally imaged in contiguous frames along the longitudinal direction that are approximately 150 microns in width and high enough to include the full thickness of the skin. Multiple texture features are being measured on a per frame basis; each feature measurement shall be reported in terms of the degree of deviation from the mean measurement made in normal skin, e.g., "percent of 200 frames deviating more than 4 SD units from the mean of the same measurement made in normal skin". Texture features include Markovian transition probability values and other functions which show the greatest deviation from the mean in normal tissues. the number of mitotic figures per mm measured along the basal layer of the esophagus shall be reported.