EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS

本工作报告的目标是探讨 通过雾化吸入化学预防药物预防肺癌。 A/J小鼠肺腺瘤模型应使用致癌物质NNK 在烟草烟雾中发现，以及B(A)P，一种非常普遍的环境 在烟草烟雾中也发现了致癌物质，但主要是由于 化石燃料的燃烧。确定药物的最大耐受量 布地奈德和苯基异硫氰酸酯(PEITC)气雾剂。“鼻子” 只是使用了曝光途径，而不是全身曝光 学习。PEITC和OltiPraz的减肺或抑肺作用 通过气雾剂暴露在A/J小鼠身上传递这些药物的癌症是 下定决心。目前使用了四种不同的剂量。小鼠被给予了 他们在8周大时第一次使用气雾剂并继续 气雾剂暴露时间为六周。实验一：在动物身上 接受暴露于PEITC的气雾剂，给予多剂量NNK 从9周大开始。实验一：在接受气雾剂的动物中 暴露于奥替拉兹，在9周龄时单次注射苯并[a]磷。 在过去的22周内继续使用化学预防药物 第一次接触致癌物质。处死小鼠，摘除肺 用于对肺部病变进行定量。对老鼠进行尸检，看看有没有其他 肉眼损伤。

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.