Morphology of respiratory tract lesions in rats exposed to radon progeny

We will discuss the morphologic features of lesions in the respiratory tract of rats exposed to radon and radon progeny. Groups of male Wister rats were exposed to from 10 to 1000 working levels (WL) of radon progeny in the presence of less than 1 to about 15 mg m-3 uranium ore dust. Cumulative exposures ranged from 20 to approximately 10,000 working level months (WLM). Higher exposure levels produced radiation pneumonitis characterized by interstitial fibrosis, associated with alveolar epithelial cell hyperplasia and accumulations of alveolar macrophages containing phagocytosed uranium ore dust. Nodular fibrosis and alveolar proteinosis were correlated with deposits of uranium ore dust. Vesicular emphysema also occurred at higher exposure levels. Pulmonary adenomatosis appeared to be a preneoplastic lesion; it was composed of nodular proliferation of bronchioloalveolar epithelium without disruption of the general architecture of the parenchyma. At exposure levels where rats lived longer than 1 y, lung tumors and a few tumors of the nasal cavity developed. The principal lung tumors were pulmonary adenomas, bronchioloalveolar carcinomas, papillary adenocarcinomas, epidermoid carcinomas, and adenosquamous carcinomas. Occasionally, malignant mesotheliomas and sarcomas were also present. The malignant lung tumors were characterized by invasion and occasionally metastasized to regional lymph nodes. Lower exposure rates produced more tumors, generally of different histologic types, and more fatal tumors than higher exposure rates. The similarity to relationships of human radon progeny exposure as far as incidence and types of lung tumors establish the validity of this animal model for studying radon carcinogenesis in humans