Toxicological Sciences, Vol 50, 64-71, Copyright © 1999 by Society of Toxicology
RW Lange, RC Lantz, DB Stolz, SC Watkins, P Sundareshan, R Lemus and MH Karol
Toluene diisocyanate (TDI), a highly reactive industrial chemical with
widespread use in the manufacture of polyurethane and plastics, is the
leading cause of occupational asthma associated with chemical exposure. We
report the effects of TDI vapor (20, 100, 500, 1000 ppb) in vitro on
differentiated human bronchial epithelial cells. Increased mucus was
observed by electron microscopy at all TDI concentrations. Cytotoxicity, as
evidenced by cell pyknosis and DNA fragmentation, was detected following a
30-min exposure to TDI concentrations of 100 ppb or higher. At 1000 ppb,
transepithelial resistance was lost. Using confocal microscopy and double
staining, TDI was found colocalized with ciliary tubulin in cultures that
had been exposed to 20 and 100 ppb. These findings are the first to
identify TDI binding to human pulmonary epithelial cells and indicate
extensive binding to the cilia of differentiated epithelial cells. The in
vivo implications of these findings include decreased ciliary movement and
longer retention of TDI and hence increased exposure. Altered
cytoskeletal-derived signal transduction may be a consequence of tubulin
involvement. The effects of such changes on respiratory sensitization
remain to be explored.
ARTICLES
Toluene diisocyanate colocalizes with tubulin on cilia of differentiated human airway epithelial cells
Department of Environmental and Occupational Health, University of Pittsburgh, Pennsylvania 15213, USA.
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