EVALUATION OF CHEMOPREVENTION AGENTS BY IN VITRO SCREENI

点击翻译按钮获取中文摘要

Chemopreventive agents which inhibit or retard the cancer process in oral mucosa are urgently needed. In order to select potential chemical candidates for whole animal and human testing, in vitro screening is required. The culture of normal oral epithelial cells and immortalized oral epithelial cell lines (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. Five log dilutions from 1 mM or the highest soluble concentration in medium or in a solvent such as dimethylsulfoxide without solvent toxicity. Three endpoints are being used to measure response to exposure to potential chemopreventive agents. Three endpoints are Ki-67, RAR- , and apoptosis. Five nontoxic concentrations (at half-log dilutions) shall be measured for their ability to modulate each endpoint. Appropriate controls shall be simultaneously tested. The criteria for a positive and negative response shall be defined in the proposal. The ED50 (50% effective dose) shall be determined by a method determined by a standard protocol. The appropriate controls shall be used.