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

该模型的目标是开发一种相对快速的方法 用NNK诱导的肺癌进行化学预防效果的测定 A系小鼠造模。这种特殊的模型会发展成肿瘤 在组织病理学上与人类腺癌和 表现出许多相同的遗传损伤，包括Rb的改变 Kiras癌基因的表达和突变。通常是这样的 化验需要在治疗后对小鼠进行为期16周的检查 NNK，然后对腺瘤的形成进行定量。在建议的新的 方法用NNK治疗小鼠，并对其进行跟踪观察 8-12周后早期组织学损害。这应该允许 一是更快地量化化学预防的效果 正在检查的化合物。总共有10种化学预防药物， 其中大约一半以前已经被完整地检查过 肿瘤试验，将在本试验中使用。其中至少有两个 糖皮质激素和苯乙基异硫氰酸酯类药物此前 在完整的16周肿瘤检测中被证明是非常有效的。

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.