EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS

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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.