EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS IN ANIMAL MOD

拟议的研究的目的是调查一系列的四种化合物的化学预防活性的4 NQO模型。 待检测的四种药剂（iNOS抑制剂、抗血管生成剂、考克斯-2抑制剂、TBA）中至少两种的MTD是已知的。 因此，仅对两种药物进行了初步毒性研究。5周龄的雄性F344大鼠计划在饮用水中随意施用20 ppm 4 NQO。 将大鼠连续维持在含有4 NQO的水上10周。 在该时间段结束时，给予大鼠常规水。 从停止4 NQO后2天开始，再给大鼠施用化学预防剂22周。 在该时间段结束时，通过CO2窒息处死大鼠。 在开始用4 NQO治疗后32周处死所有大鼠。 尸检时，对各种其他组织，特别是口腔组织进行大体检查。 将大鼠的舌头固定在福尔马林中。 口腔的其他组织被固定在福尔马林中。 对于组织病理学确认，应将组织和大体病变固定在10%缓冲福尔马林中，包埋在石蜡块中，并使用H&E染色通过常规组织学方法进行处理。

The objectives of the proposed studies will be to investigate a series of four compounds for chemopreventive activity in the 4NQO model. The MTDs of at least two of the four agents to be examined (iNOS inhibitor, antiangiogenic agent, Cox-2 inhibitor, TBA) are known. Therefore preliminary toxicity studies are being performed on only two agents. Five week old male F344 rats are scheduled for administration 20 ppm 4NQO in the drinking water ad libitum. Rats are being maintained continually on 4NQO containing water for a period of 10 weeks. At the end of this time period rats regular water is given. Starting 2 days following the cessation of 4NQO rats are being given chemopreventive agents for an additional 22 weeks. At the end of this time period rats are being sacrificed by CO2 asphyxiation. All rats are sacrificed 32 weeks following the initiation of treatment with 4NQO. At necropsy various other tissues, particularly of the oral cavity, are being examined grossly. Tongues of rats are fixed in formalin. Other tissues of the oral cavity are fixed in formalin. For histopathologic confirmation, tissues and gross lesions shall be fixed in 10% buffered formalin, embedded in paraffin blocks and processed by conventional histologic methods using H&E staining.