The cellular events which occur in the transformation from normal bladder epithelium to transitional cell carcinoma are not understood. Numerous animal models have been employed to study bladder cancer, but they have the inherent limitation of the inability to study the metabolism of a single cell type during disease processes. To facilitate understanding of how a specific cell is altered during carcinogenesis, an in vitro model system must be defined. The proposed studies describe the development and characterization of such an in vitro system. Conditions will be defined for serial cell culture of both normal and transformed transitional epithelial cells for which an in vivo system is available for comparison. Correlation of in vivo and in vitro model systems is essential for determining the validity of the culture system for future studies. The primary goals of these studies are: (1) to establish, in a serum-free growth medium, transitional epithelial cells derived from normal mouse bladder; (2) to define the optimal growth conditions for transitional cell carcinoma epithelial cells from the same strain of mouse; (3) to correlate the mouse in vivo and in vitro systems employing a battery of morphologic techniques, including enzyme and carbohydrate histochemistry and electron microscopy; and (4) to employ this cell culture system to investigate cellular metabolism with emphasis on preneoplastic events and metabolism of antineoplastic retinoid compounds. The successful completion of these efforts will yield a model system for the study of transitional epithelial cell characteristics in normal and disease situations. An increased understanding of the metabolic activities of these cells when exposed to carcinogens and retinoids will yield new insights of importance regarding the carcinogenic process.
