Animal models for chemoprevention of respiratory cancer

Of the several models for lung carcinogenesis, two appear appropriate for chemoprevention studies based upon dose response, tumor type, and tumor localization. One model utilizes the direct-acting carcinogen methylnitrosourea (MNU), and the other utilizes a carcinogen (diethylnitrosamine) requiring metabolic activation. Tumors appear rapidly in both models (within 6 months), and the model systems are responsive to modulation by several classes of potential chemopreventive agents. For example, the retinoid N-(4-hydroxyphenyl) retinamide reduces the incidence of lung adenosquamous carcinoma, but retinol or beta-carotene are ineffective when administered alone. However, concomitant administration of these compounds reduces the incidence of non-neoplastic dysplasias as well as adenosquamous carcinomas of the lung. In the MNU system, retinoids in general have been ineffective in reducing the incidence of tracheobronchial squamous-cell carcinomas.