SCREENING POTENTIAL CHEMOPREVENTIVE AGENTS IN MICE

在小鼠中筛选潜在的化学预防剂

• 批准号: 6165873
• 负责人: Clinton Julian Grubbs
• 金额: --
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-30 至 2000-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6165873
• 关键词: adenomatous polyps; animal breeding; cancer prevention; carcinogenesis inhibitor; chemoprevention; colorectal neoplasms; disease /disorder model; drug screening /evaluation; gene mutation; laboratory mouse; model design /development; neoplasm /cancer genetics

The primary objective of this workstatement is to investigate the chemopreventive efficacy of a variety of agents employing transgenic animals which have mutations similar to those found in humans and which spontaneously develop colon tumors. The first mouse model (Min mouse) has a mutation in the APC gene and develops multiple adenomas in a manner analogous to human FAP (familial adnomatous polyposis) patients. These mice will be employed to screen for four different potential chemopreventive agents. In addition two highly effective aspects will be employed to determine whether these agents are still effective one early, pre invasive, adenomas have arisen. The second animal model has a deficiency in the repair gene MSH-2 and appear comparable to humans with HNPCC (hereditary nonpolyposis colon cancer). These mice will be bred containing both APC and MSH-2 mutations will be bred and will be examined for chemopreventive efficacy employing a variety of chemopreventive agents. The results of these animal studies, employing these directly relevant models, are likely to be immediately applicable in determining agents for potential human trials.

此工作声明的主要目标是调查 多种转基因药物的化学预防效果 具有与人类相似的突变的动物 自发性地发展成结肠癌。第一个鼠标模型(Min鼠标)具有 APC基因突变，并以某种方式发展为多发性腺瘤 类似于人类家族性息肉病(FAP)患者。这些 老鼠将被用来筛选四种不同的潜力 化学防护剂。此外，两个高度有效的方面将是 用来确定这些代理人是否仍然有效的一个早期， 在侵袭前，腺瘤已经出现。第二个动物模型有一个 修复基因MSH-2缺乏，看起来与患有 遗传性非息肉病性结肠癌。这些小鼠将被培育出来 同时含有APC和MSH-2突变的将被培育并将被检测 使用各种化学预防措施来实现化学预防效果 探员们。这些动物研究的结果，直接利用这些 相关模型，很可能立即适用于确定 潜在人体试验的代理人。