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© 1993 Oxford University Press

research-article

Autoradiographic Analyses of Guinea Pig Airway Tissues Following Inhalation Exposure to 14C-Labeled Methyl Isocyanate

AMY L. KENNEDY*, GURMUKH SINGH{dagger}, YVES ALARIE{ddagger} and WILLIAM E. BROWN*

*Department of Biological Sciences, Carnegie Mellon University Pittsburgh Pennsylvania 15260 {dagger}Department of Pathology and Laboratory Service, VA Medical Center, University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania 15260 {ddagger}Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh Pittsburgh, Pennsylvania 15261

Received March 9, 1992; accepted August 5, 1992

Through the use of radioactively labeled methyl isocyanate (MIC), the deposition, penetration, and clearance of this highly reactive compound in the airway at the tissue and cellular levels have been directly examined. Guinea pigs were exposed to 14C-MIC vapors at concentrations ranging from 0.38 to 15.2 ppm for periods of 1–6 hr. Solubilization of tissues from these animals showed the airway tissues to have the highest level of radioactivity. In the nasal region, 14C deposition, as monitored by histoautoradiography, was limited to the epithelial layer, was related to dose, and was dependent on the specific epithelial cell type. The squamous epithelium was minimally labeled on the surface and the label did not penetrate the cell layer. However, radioactivity was detected throughout the entire nasal respiratory epithelial layer. The lack of nasal deposition in tracheotomized animals demonstrated that the 14C accumulation at this site was due to the scrubbing action of the nasal region with no contribution from blood recirculation. Cellular localization in the tracheobronchial region showed epithelial and subepithelial deposition in a dose-dependent manner with accumulation of the label at the subepithelial region. Radioactivity penetrated to the level of the terminal bronchiole but was not detected in the alveolar region. The persistence of airway radioactivity over the 48-hr postexposure period monitored suggests the covalent modification of airway macromolecules. Despite its broad specificity and high reactivity, MIC undergoes selective reactions in the airways which are dependent on respiratory region and cell type.


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