TRANSITIONAL CELL CARCINOMA: IN VITRO/IN VIVO CORRELATES

正常膀胱转化过程中的细胞事件 上皮癌到移行细胞癌目前尚不清楚。数不胜数 动物模型已经被用来研究膀胱癌，但他们有 不能研究单个人的新陈代谢的固有局限性 疾病过程中的细胞类型。为了便于理解 特定细胞在致癌过程中发生改变，这是一个体外模型系统 必须被定义。拟议的研究描述了发展和 这种体外系统的特征。将定义条件 适用于正常和转化的移行细胞的连续培养 有活体系统可供比较的上皮细胞。 体内和体外模型系统的相关性对于 为今后的研究确定培养体系的有效性。 这些研究的主要目标是：(1)建立一种无血清 正常小鼠移行上皮细胞生长培养液 (2)确定移行细胞的最佳生长条件 来自同一品系小鼠的癌细胞；(3)相互关联 利用一组形态电池的小鼠体内和体外系统 技术，包括酶和碳水化合物组织化学和电子 显微镜下观察；(4)利用该细胞培养系统研究 细胞代谢，重点是癌前事件和新陈代谢 抗肿瘤类维甲酸化合物。 这些工作的成功完成将产生一个模型系统 正常人和正常人移行上皮细胞特性的研究 疾病状况。增加对新陈代谢活动的了解 当这些细胞暴露在致癌物和维甲酸中时，会产生新的 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.