RESPIRATORY CARCINOGENESIS BY CHEMICAL AND PHYSICAL FACTORS

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Foci of lung alveolar type II epithelial hyperplasia and adenomatoid lesions, adjacent to areas of fibrosis, were found in 4 human cases of silicosis, including 2 with lung cancer, out of a series of 24 cases of coalworkers' pneumoconiosis or silicosis. The hyperplastic alveolar type II cells showed marked immunoreactivity to antibodies against TGF-~1 latency-associated peptide, similar to that previously described in rats treated with a single intratracheal instillation of crystalline silica (quartz), and considered as preneoplastic lesions. Further histologic study of the National Coalworkers Autopsy Study archive at the National Institute for Occupational Safety and Health (NIOSH), Morgantown, WV, has detected numerous additional cases of alveolar type II hyperplasia adjacent to fibrotic lesions and dust deposits. A pilot study has been designed and set up, in collaboration with NIOSH and with the Epidemiology and Biostatistics Program, DCE, NCI, in order to examine the occurrence of the epithelial proliferative lesions and lung cancers by histologic type in a large population of uranium miners from the Saxony region in Germany, who received heavy exposures to silica and/or radiation especially in the 1950s and '60s. Over 15,000 cases of silicosis and 5,000 cases of lung cancer have already been identified in this population, for which there are available exposure histories and autopsy records for over 90% of cases. In a study of the largest reported series of clinical association of cancers of the larynx and lung, the lung cancers associated with squamous carcinomas of the larynx showed different histologic types (70% squamous carcinomas, 11% adenocarcinomas and 6% small cell carcinomas), indicating that differentiation may vary in carcinogenesis of multiple respiratory tract malignancies. Rats treated with a single intrabronchial instillation of 1.25 mg quartz and previously reported to show electron microscopic localization of quartz particles in alveolar epithelial cells were sacrificed at 15 months and showed foci of interstitial pulmonary fibrosis. Fragments of their lungs were explanted and subcultured, originating new rat lung epithelial cell lines.