EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS

化学预防剂的功效研究

• 批准号: 6131190
• 负责人: MICHAEL A. PEREIRA
• 金额: $ 25.95万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-15 至 2001-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6131190
• 关键词: antiinflammatory agents; antineoplastics; azo compounds; cancer prevention; carcinogenesis inhibitor; chemoprevention; colon neoplasms; drug screening /evaluation; enzyme inhibitors; histology; laboratory rat; light microscopy; lipoxygenase; nitric oxide synthase

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.

使用雄性Fisher 344大鼠研究各种化学预防药物减少或抑制结肠癌的效果。根据Tudek，Bird和Bruce的方法(癌症研究49：1236-1240,1989)，在第一次致癌物质暴露四周后测量异常隐窝的形成。这些大鼠接受了标准的半纯AIN-76A饮食，每公斤体重间隔一周注射两次15毫克的偶氮甲烷(AOM)。从第一次致癌物治疗前一周和治疗后四周开始，给大鼠服用试验性化学预防药物。然后杀死老鼠并对畸形的隐窝进行划痕(见伯德，癌症快报，37：147-151,1987)。对于这两种方案，在光学显微镜下对每个结肠的异常隐窝病灶数和未切开的亚甲蓝染色结肠的每个病灶的异常隐窝数进行评分。所有小组都进行了编码，小组由两个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，以确定各种药剂增强或抑制效果的重要性。正在研究的药物类别包括脂氧合酶抑制剂、一氧化氮合酶抑制剂、新型抗炎药以及这些药物和其他药物的组合。