The purpose of the project is to prepare serial cytology smears from brushings of rat esophageal epithelium and corresponding histological sections from esophagi undergoing intraepithelial progression from submicroscopic predysplastic changes to intraepithelial neoplasia (IEN) to papillomas in response to the carcinogen nitrosomethylbenzylamine (NMBA). In the cytology smears and histological sections, the study is quantitatively following the changes in nuclear features by computer-assisted image analysis. They are also following the extent of regression of established intraepithelial neoplasia produced by the chemopreventive agent phenylethyl- isothiocyanate and by theaflavin, curcumin, difluoromethylornithine (DFMO) and a combination of curcumin and DFMO. A special rat esophageal cytology brush is being used. The brush is passed along the esophagus of lightly anesthetized rats and the adhering cells swished into physiological saline solution. The cells are then collected by centrifugation and smears of the cells are prepared using the MonoGen, Inc., method of preparing uniform cell monolayers without overlapping cells. The administration of chemopreventive agents begins 8 weeks after start of carcinogen (3 weeks after stop of carcinogen) and is continued until the end of the study at 20 weeks after start of carcinogen.
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