The proposed investigation is a correlated morphological and cytochemical approach to the detection of abnormalities in the colon of the rat following administration of a carcinogen. We plan to use the animal model in which approximately 70% of rats given a single intravenous injection of methylazoxymethanolacetate (MAM-acetate) develop adenocarcinomas of the descending colon, within seven months after injection. Induction of tumors by this means appears to be a satisfactory model for colon cancer in man. The following methods will be used on normal colon, colonic tumors and mucosa adjacent to tumors: procedures for the 1) localization of enzyme activities that are associated with cell organelles 2) localization of plasma membrane-associated enzyme activities 3) localization of mucosubstances 4) detection of permeability changes in the plasma membrane with peroxidase as a probe molecule 5) detection of lectin-receptor sites in the cell surface with concanavalin A complexed to peroxidase or ferritin 6) transmission electron microscopy of colon cells and scanning electron microscopy of the surface epithelium. The principal aim is to determine whether these procedures are of value in detecting abnormalities of the colon in rats given a carcinogenic dose of MAM-acetate.
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