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Morphological and Cytokinetic Responses of Hamster Airways to Intralaryngeal or Intratracheal Cannulation with Instillation of Saline or Ferric Oxide Particles in Saline¹

Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201 [K. P. K., E. M. M.]; Laboratory of Experimental Pathology, Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20892 [U. S., S. F. S.]; and Computer and Statistical Services, Data Management Services, Inc., National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland 21701 [C. W. R.]

The morphological and proliferative effects of intratracheal cannulation (ITC) or intralaryngeal cannulation (ILC), with or without the instillation of saline or Fe₂O₃ particles in saline, were studied in Syrian golden hamsters. Instillation of Fe₂O₃ in saline at either airway level resulted in a similar distribution of Fe₂O₃ particles in all lung lobes. ILC produced laryngeal mucosal wounds. ITC produced laryngeal and tracheal mucosal wounds. The cannula-induced wounds were associated with proliferative epithelial lesions. ITC, but not ILC, resulted in significant increases in the mitotic rates (MR, 6-h colchicine blockade) of tracheal epithelial cells at 24 and 32 h postcannulation. Instillation of saline by ITC produced slight increases in intrapulmonary bronchial and bronchiolar MR, but saline given by ILC did not increase MR at any airway level. Instillation of Fe₂O₃ particles in saline by ITC produced increases in tracheal, intrapulmonary bronchial, and bronchiolar MR. Instillation of Fe₂O₃ particles in saline by ILC had little effect on tracheal MR, but increased intrapulmonary bronchial and bronchiolar MR. Foci of Fe₂O₃ particle-laden macrophages were associated with mild bronchiolar-alveolar hyperplasia at the junctions of the terminal bronchioles and the alveolar ducts. The cytokinetic and morphological changes in the intrapulmonary airways were associated with the influx of inflammatory cells in response to Fe₂O₃ particle deposition. The marked increases in tracheal MR and the localized hyperplastic tracheal epithelial lesions were clearly associated with mechanical wounding from the cannula during ITC. Comparative studies using ILC or ITC instillation techniques allowed further investigations of the important role of tracheal mucosal wounding in the induction of respiratory carcinogenesis, as described in a companion paper (Keenan et al., Cancer Res., 49: 1528–1540, 1989).

¹ Supported by National Cancer Institute Contract N01-CP-26505 [E. M. M.] and a Pharmaceutical Manufacturers Association Faculty Development Award [K. P. K.]

² Present address: Department of Safety Assessment, Building WP44-1, Merck Sharp and Dohme Research Laboratories, West Point, PA 19486.

³ To whom requests for reprints should be addressed, at Department of Pathology, University of Maryland School of Medicine, 10 South Pine Street, Baltimore, MD 21201.

Received 4/22/88. Revised 11/14/88. Accepted 12/13/88.

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