EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS

目前正在研究各种化学预防剂减少或抑制雄性Fisher 344大鼠结肠癌的功效。根据Tudek， Bird和Bruce （Cancer Research 49:1236-1240, 1989）的方法，在首次接触致癌物四周后测量异常隐窝形成。这些大鼠喂食标准的半纯化AIN-76A饲料，每公斤体重注射15毫克氮氧甲烷（AOM），间隔一周。在第一次致癌物治疗前一周和治疗后四周给大鼠注射化学预防试验剂。然后杀死老鼠并记录异常的隐窝（见Bird， Cancer letter .37:147-151, 1987）。对于两种方案，在光镜下对每个结肠的异常隐窝病灶数量和未切片亚甲蓝染色结肠的每个病灶的异常隐窝数量进行评分。所有分组都被编码，分组由两名独立的评分员以盲法评分。对所有数据进行适当的统计分析，以确定各种药物增强或抑制作用的重要性。正在研究的药物类别包括脂氧抑制剂、INOS抑制剂、较新的抗炎药物以及这些药物和其他药物的组合。

The efficacy of a variety of chemopreventive agents to reduce or inhibit colon cancer using male Fisher 344 rats is being studied. Aberrant crypt formation is being measured four weeks after the first carcinogen exposure, according to methods of Tudek, Bird, and Bruce (Cancer Research 49:1236-1240, 1989). The rats are being standard semi-purified AIN-76A diet and given two injections of 15 mg of azoxymethane (AOM) per kg of body weight one week apart. The test chemopreventive agent are given to the rats from one week prior to and four weeks following the first carcinogen treatment. Then kill the rats and score the aberrant crypts (see Bird, Cancer Lett.37:147-151, 1987). For both protocols, the number of aberrant crypt foci per colon and the number of aberrant crypts per foci from unsectioned methylene-blue stained colons are scored under light microscopy. All groups are coded and groups are scored in a blinded manner by two independent scorers. Perform an appropriate statistical analysis on all data to determine significance of enhancing or inhibiting effects of the various agents. The classes of agent being studied include lipoxyganse Inhibitors, INOS inhibitors, newer antiinflammatory agents and combinations of these and other agents.