Differential labelling of airway epithelial cell types resulting from inhalation exposure to 14C-labelled isocyanates.
Brown WE; Kennedy AL; Alarie Y; Singh G
Am Rev Respir Dis 1992 Apr; 145(4)(Pt 2)(Meeting Abstracts):A359
Isocyanates are widely used commercial chemicals which have been associated with airway diseases in humans and animal models. In general, the primary target for reactive gases and vapors is the respiratory tract; however, limited detailed information is available regarding retention sites of these molecules. Through the use of radioactively labelled methyl isocyanate (MIC) and toluene diisocyanate (TDI), the deposition, penetration and clearance of these highly reactive compounds in the airway at the tissue and cellular levels have been directly examined. Guinea pigs were exposed to dynamic atmospheres of 14C-MIC and 14C-TDI vapors at concentrations ranging from 0.38 to 15.2 ppm and 0.004 ppm to 0.15 ppm, respectively, for periods from 1-6 hrs. Solubilization of tissues from these animals showed the airway tissues to have the highest level of radioactivity. Independent of the isocyanate used, 14C deposition in the nasal region, as monitored by histoautoradiography, was limited to the epithelial layer, was related to dose and was dependent on the specific epithelial cell type. The more resistant, squamous epithelium was labelled on the cell surface. Radioactivity was detected throughout the entire respiratory epithelial layer and this cell type was the site of greatest accumulation of 14C in the nasal cavity. Olfactory epithelial cells in the posterior nasal region were minimally labelled. 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. At comparable exposure concentrations, radioactivity penetrated to the level of the terminal bronchioles but was not detected in the alveolar region. Persistence of post-exposure, airway radioactivity suggests the covalent modification of airway macromolecules. Despite their high degree of chemical reactivity, both TDI and MIC undergo selective reactions in the airways which are dependent on the respiratory region and epithelial cell type.
Isocyanates; Respiratory-system-disorders; Laboratory-animals; Laboratory-techniques; Laboratory-testing; Radioactivation-analysis; Reaction-rates; Exposure-levels; Exposure-methods; Vapors; Dose-response; Airway-obstruction; Cellular-reactions; Nasal-cavity; Tissue-culture; Cell-cultures; Histochemical-analysis; Radiography
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213
American Review of Respiratory Disease
Carnegie-Mellon University, Pittsburgh, Pennsylvania