EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS

本工作说明的目的是探讨 通过化学预防剂的气溶胶递送预防肺癌。 A/J小鼠肺腺瘤模型应与致癌物NNK一起使用 在烟草烟雾中发现，和B（a）P，一种高度普遍存在的环境 致癌物质也发现在烟草烟雾，但主要是由于 化石燃料的燃烧。确定最大耐受剂量 布地奈德和异硫氰酸苯乙酯（PEITC）气雾剂。 “鼻子 仅使用”暴露途径，而非全身暴露 问题研究PEITC和奥替普拉减少或抑制肺部的功效 在A/J小鼠中通过气溶胶暴露递送这些药剂的癌症正在被 测定使用了四种不同的剂量。 给老鼠 在8周龄时首次使用气雾剂， 暴露在气雾剂中六周。实验I：动物 接受PEITC气雾剂暴露，给予多剂量NNK 从9周龄开始。实验II：接受气雾剂的动物 暴露于奥替普拉，在9周龄时给予单剂量的B[a]P。 持续使用化学预防剂22周 第一次接触致癌物。处死老鼠，取出肺 用于定量肺部病变。对老鼠进行尸检， 肉眼病变。

The objective of this workstatement is to explore the strategy of preventing lung cancer by aerosol delivery of chemopreventive agents. The A/J mouse lung adenoma model shall be used with NNK, a carcinogen found in tobacco smoke, and B(a]P, a highly ubiquitous environmental carcinogen also found in tobacco smoke, but primarily due to the combustion of fossil fuels. Determine the maximum tolerated dose for budesonide and phenethylisothiocyanate (PEITC) given by aerosol. "Nose only" exposure route is being used, not whole body exposure for these studies. The efficacy of PEITC and Oltipraz to reduce or inhibit lung cancer delivering these agents by aerosol exposure in A/J mice is being determined. Four different doses are being used. The mice are given their first aerosol administration at eight week of age and to continue aerosol exposure for a period of six weeks. Experiment I: in animals receiving aerosol exposure to PEITC, give multiple doses of NNK beginning at 9 weeks of age. Experiment Il: in animals receiving aerosol exposure to oltipraz, give a single dose of B[a]P at 9 weeks of age. Continue the administration of chemopreventive agent for 22 weeks past the first carcinogen exposure. Sacrifice the mice and remove the lungs for quantitation of pulmonary lesions. Autopsy the mice for any other gross lesions.