EFFICACY OF CHEMOPREVENTIVE AGENTS IN ANIMAL MODELS

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The problem of delivering chemopreventive drugs to the target site of action in their unmetabolized, highly concentrated form is an area of research where clearly more attention needs to be focused. In the case of pulmonary tissue, one clear option for drug delivery is the inhalation of aerosols containing chemopreventive agents. Recently the aerosolized administration of budesonide has been shown to markedly inhibit B[a]P induced adenoma formation in lungs of the Strain A mouse. The objective of this workstatement is to investigate the mechanisms and efficacy and explore the strategy of preventing lung cancer by aerosol delivery of chemopreventive agents. The A/J mouse lung adenoma model shall be used with B[a]P, a highly ubiquitous environmental carcinogen found in tobacco smoke, but primarily due to the combustion of fossil fuels. The agent being tested is a 5- lipoxygenase inhibitor. A rangefinding study is first being conducted to find the highest nontoxic dose. This dose plus one lower dose are being tested using inhalation administration. The frequency of lung adenomas per animal is being used as the endpoint in this study.