INHIBITION OF 4-METHYLNITROSAMINO-3-PYRIDYL-1-BUTANONE

该模型的目的是开发一种相对快速的方法， 使用NNK诱导的肺肿瘤确定化学预防功效 A系小鼠模型。 这种特定的模型会产生肿瘤 组织病理学上类似于在人腺癌中观察到的那些， 表现出许多相同的遗传病变，包括RB的改变， 表达以及KiRas癌基因中的突变。 通常这 测定需要在治疗后检查小鼠16周的时间 与NNK，然后定量腺瘤形成。 拟议新订 方法学小鼠将用NNK处理，并跟踪其发展。 8-12周后出现早期组织学病变。 这应该允许 一种可以更快地定量化学预防功效的方法 正在检查的化合物。 总共10种化学预防剂， 其中大约一半以前已经在一个完整的 肿瘤测定法将用于本测定法。 这些中至少两 药物糖皮质激素和异硫氰酸苯乙酯以前 在完整的16周肿瘤测定中显示出高度有效。

The objective of this model is to develop a relatively rapid method for determining chemopreventive efficacy employing the NNK-induced lung tumor model in strain A mice. This specific model develops tumors histopathologically similar to those observed in human adenocarcinomas and exhibit many of the same genetic lesions including alterations in RB expression as well as mutations in the KiRas Oncogene. Typically this assay entails examining mice for a period of 16 weeks following treatment with NNK and then quantitating adenoma formation. In the proposed new methodology mice will be treated with NNK and followed for development of early histologic lesions after a period of 8-12 weeks. This should allow one to more rapidly quantitate the chemopreventive efficacy of the compounds under examination. A total of 10 chemopreventive agents, approximately half of which have previously been examined in a complete tumor assay, will be employed in the present assay. At least two of these agents glucocorticoid and phenethylisothiocyanate have previously been shown to be highly effective in the complete 16 week tumor assay.