SCREENING POTENTIAL CHEMOPREVENTIVE AGENTS IN MICE

本工作说明的主要目的是调查 使用转基因的多种试剂的化学预防功效 动物具有与人类相似的突变， 自发地发展结肠肿瘤。 第一个小鼠模型（Min小鼠）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FAP（家族性腺瘤性息肉病）患者。 这些 小鼠将被用来筛选四种不同的潜力， 化学预防剂 此外，两个非常有效的方面将是 用于确定这些试剂是否仍然有效， 在侵袭之前，已经出现了腺瘤。 第二种动物模型具有 缺乏修复基因MSH-2，似乎与人类相当， HNPCC（遗传性非息肉病性结肠癌）。 这些老鼠将被繁殖 将培育含有APC和MSH-2突变的小鼠， 对于采用多种化学预防剂的化学预防功效， 剂. 这些动物研究的结果，直接使用这些 相关模型，很可能立即适用于确定 用于潜在的人体试验。

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.