IN VITRO SCREENING OF POTENTIAL CHEMOPREVENTIVE AGENTS

正常口腔上皮细胞和永生化口腔上皮细胞的培养 已经发表了上皮细胞系(例如参见Xu等人， 细胞科学方法18：31-39,1996和萨克斯、癌症和 转移回顾，15：27-51,1996)。这样的文化或最好是 发育不良的口腔上皮细胞被用来筛选潜在的 化学防护剂。最初的生长抑制或其他 目前存在的测试化学预防药物的细胞毒性分析是 用于选择适当的浓度范围以用于 随后进行转化抑制试验。归纳的水平 三个与抑制、反转或 延缓癌症进程，以应对潜在的暴露 目前正在探索化学预防药物。正常口腔上皮 细胞和永生化口腔上皮细胞系(口腔发育不良 上皮细胞)正被用于筛选潜在的化学预防 探员们。选择的端点可以量化为 回应。应测量至少三个端点以响应 化学防护剂。终结点包括：单元延迟 循环，谷胱甘肽含量增加，并诱导细胞凋亡， 倍体、增殖指数(增殖细胞核抗原、BrdU)、Ki-67、MIB-1、 P53、KS-5、核多形指数、RAR-β、转化生长因子-β和 微核。适当的控制措施正在同时进行测试。 ED50(50%有效剂量)正在用一种方法测定 由标准协议确定。

The culture of normal oral epithelial cells and immortalized oral epithelial cell lines has been published (for example see Xu et al., Methods in Cell Science 18:31-39, 1996 and Sacks, Cancer and Metastasis Review, 15:27-51, 1996). Such cultures or preferably dysplastic oral epithelial cells are being used to screen potential chemopreventive agents. Initial growth inhibition or other cytotoxicity assays with the test chemopreventive agent present are being used to select appropriate concentration ranges for use in the subsequent transformation-inhibition assays. The levels of induction of three endpoints associated with inhibiting, reversing, or retarding the cancer process in response to exposure to potential chemopreventive agents are being explored. Normal oral epithelial cells and immortalized oral epithelial cell lines (dysplastic oral epithelial cells) are being used to screen potential chemopreventive agents. The endpoints chosen are amenable to quantitation of response. At least three endpoints shall be measured for response to chemopreventive agents. The endpoints include: retardation of cell cycle, increased glutathione content, and induction of apoptosis, changes in ploidy, proliferative index (PCNA, BrdU), Ki-67, MiB-1, p53, KS-5, nuclear pleomorphism index, RAR-beta, TGF-beta, and micronuclei. Appropriate controls are being simultaneously tested. The ED50 (50% effective dose) are being determined by a method determined by a standard protocol.