| Rat Pleural Mesothelial Cells Show Damage after Exposure to External but Not Internal Cigarette Smoke Harmanjatinder S. Sekhon, Beverley Keeling, and Andrew Churg Department of Pathology and University Hospital, University of British
Columbia, Vancouver, BC, Canada. Abstract
The combination of cigarette smoke and high-level occupational asbestos exposure produces a synergistic increase in the incidence of lung cancer ; however, smoking does not affect the incidence of mesothelioma. Here we present the results of tests of two theories that have been proposed to explain this phenomenon ; namely, that pleural mesothelial cells are resistant to cigarette smoke-induced damage and that the pleural connective tissue acts as a barrier that prevents smoke from reaching the mesothelial cells. To test these hypotheses, excised whole rat lung preparations were exposed to either internal (intratracheal) or external (pleural surface) smoke. For comparison, additional excised lung preparations were exposed to solutions of hydrogen peroxide either externally or intratracheally. Mesothelial cells exposed to external smoke showed widespread, dose-dependent,uptake of Trypan blue. Mesothelial cells did not take up Trypan blue after exposure to internal smoke. Bronchial epithelial cells exposed to internal smoke did show uptake, but to a lesser degree than externally exposed mesothelial cells. Examination by scanning and transmission electron microscopy showed that internal smoke did not affect mesothelial cell ultrastructure, whereas external smoke produced obvious mesothelial cell damage and mesothelial cell detachment. Catalase and deferoxamine, scavengers of active oxygen species, provided protection against smoke-induced mesothelial cell injury, but inactivated catalase did not. External hydrogen peroxide produced a very similar, dose-dependent pattern of Trypan blue uptake and ultrastructural changes. Intratracheal hydrogen peroxide also damaged mesothelial cells, but the extent of damage was always less than with comparable concentrations of external hydrogen peroxide. We conclude that 1) pleural mesothelial cells are sensitive to damage by smoke-derived active oxygen species ; 2) the pattern of injury is similar to that produced by hydrogen peroxide ; 3) bronchial epithelial cells appear to be less sensitive to smoke-induced oxidant damage than mesothelial cells ; and 4) at least acutely, the pleura appears to act as a barrier to smoke and penetration of active oxygen species. Key words: active oxygen species, catalase, cigarette smoke, deferoxamine, mesothelial cells. Environ Health Perspect 101:000-000(1993) Address correspondence to A. Churg, Department of Pathology, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5. H.S. Sekhon is a Fellow of the Canadian Lung Association. This study was supported by the Medical Research Council of Canada grants MA8051 and MA7820.
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