EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS

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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 (Wattenberg et al., Cancer Res. 57:5489-5492, 1997). The objective of this study is to investigate the efficacy of four chemopreventive agents including Difluoromethylornithine (DFMO) and Beclomethasone dipropionate to inhibit lung cancer in this model. The Syrian Golden lung cancer model is being used with MNU, a carcinogen known to induce squamous cell carcinomas. Chemopreventive agents are being delivered by aerosol. At 30 weeks after the beginning of MNU administrations the hamsters are being assayed for pulmonary lesions and carcinoma 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.