TRANSITIONAL CELL CARCINOMA: IN VITRO/IN VIVO CORRELATES

正常膀胱转化过程中发生的细胞事件 上皮细胞到移行细胞癌的关系尚不清楚。 许多 动物模型已被用于研究膀胱癌，但他们有 无法研究单一代谢的固有局限性 疾病过程中的细胞类型。 为了便于理解 特定细胞在癌发生过程中发生改变，体外模型系统 必须定义。 拟议的研究描述了发展和 这种体外系统的表征。 将定义条件 对于正常的和转化的过渡细胞的连续细胞培养， 上皮细胞，其体内系统可用于比较。 体内和体外模型系统的相关性对于 为今后的研究确定文化系统的有效性。 这些研究的主要目的是：（1）建立，在无血清 生长培养基，来自正常小鼠的移行上皮细胞 膀胱移行细胞的最佳生长条件 同一品系小鼠的癌上皮细胞;（3） 小鼠体内和体外系统采用一组形态学 技术，包括酶和碳水化合物组织化学和电子 显微镜;和（4）使用这种细胞培养系统来研究 细胞代谢，重点是肿瘤前事件和 类维生素A化合物。 这些努力的成功完成将产生一个示范系统， 正常人和正常人膀胱移行上皮细胞特性研究 疾病情况。 增加对代谢活动的了解 当这些细胞暴露于致癌物质和类维生素A时， 关于致癌过程的重要见解。

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.