Histologic Characterization of Mouse Bronchiolar Cell Hyperplasia, Metaplasia, and Neoplasia Induced Intratracheally by 3-Methylcholanthrene

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Abstract
Female B6C3F1 mice were treated intratracheally with 3-methylcholanthrene (MCA) at intervals of once every 2 weeks for a total of six doses each of 222 μg or 457 μg/mouse per dose. Animals were necropsied when found dead, moribund, or at the end of the study 43 weeks after the first treatment. Controls were treated with the vehicle (0.2% gelatin saline) only. Lungs were fixed in neutral buffered formalin and processed for light microscopic evaluation. Proliferative and metaplastic bronchiolar cell alterations were seen both within bronchioles and in the alveolar parenchyma. In both locations, changes included hyperplasia of nonciliated cells, squamous cell metaplasia, presence of ciliated cells, and mucous cell metaplasia. Mucous cells were either positive for alcian blue or the periodic-acid Schiff's reaction (PAS), or appeared eosinophilic with hematoxylin and eosin (H&E) but colorless with PAS. Tumors seemed to develop from both extra- and intrabronchiolar areas of cellular proliferation and invaded pulmonary structures. The majority were squamous cell carcinomas and adenosquamous carcinomas, accompanied by a few mucinous cell tumors and some rare tumors that were largely composed of ciliated cells. Combinations of the different metaplastic changes were frequently present in these neoplasms. In summary, it appears that tumors originating from bronchiolar cells in mice show the same morphologic variability that is observed in hyperplastic and metaplastic bronchiolar cells within airways.