EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS IN ANIMAL MOD

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The feasibility of aerosol drug delivery strategy for the chemoprevention of pulmonary cancer has been validated recently. This route of exposure has the added advantage of applying a high concentration of agent to the target tissue while theoretically minimizing attending systemic toxicity. Certainly the route of exposure of the pulmonary epithelia to carcinogens is overwhelmingly due to inhalation of particulates, aerosolized liquids, or gases. 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 study is to investigate the efficacy of four chemopreventive agents including: difluoromethylornithine (DFMO) (aerosol), zileuton (diet and aerosol), sulindac, and combinations of DFMO and budesonide, and sulindac and budesonide to inhibit lung cancer in this model. The Strain A Mouse lung cancer model is being used with benzo[a]pyrene, a carcinogen known to induce lung adenomas. Chemopreventive agents are being primarily delivered by aerosol. At 16 weeks after the beginning of B[a]P administrations the mice are being assayed for pulmonary lesions and adenoma formation. The number of animals with lung tumors, the number of lung tumors per animal, and the number of lung tumors per tumor-bearing animal is recorded. All tumors are excised and examined histologically and a pathological diagnosis made on each tumor.