Proliferation of lung and airway cells induced by nitrogen dioxide

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Abstract
Proliferation of lung cells of Chinese hamsters was examined in several regions of the lung parenchyma and ciliated airway epithelium after a 24‐h exposure to 28.2 mg/m 3 (15 ppm) nitrogen dioxide (NO 2 ). Label was retained 3 wk after the injection of [ 3 H]thymidine, and autoradiographic methods were used to localize the site of retention. By 24 h after administration of [ 3 H]thymidine, parenchymal areas, exclusive of airways, showed an increased labeling index, indicative of cell death and replacement. This increase in the number of labeled cells persisted for 3 wk. Type II cells were labeled twice as frequently in regions of the terminal bronchiole than in other alveolar areas. Type II cell cycle time was reduced from 26 to 3 d after NO 2 exposure. Alveolar macrophages were significantly labeled in the alveolar areas during the thymidine pulse at the end of the exposure episode and retained label for 3 wk. Airway epithelia showed no labeling in the trachea and progressively greater labeling in increasingly smaller airways. Epithelial cells lining the small airways and alveoli showed greater susceptibility to NO 2 injury than cells lining the bronchi or trachea. Nonciliated or basal cells serve as a precursor of ciliated cells in the epithelium of small airways (0.35 mm) and bronchi.