RAT PLEURAL MESOTHELIAL CELLS SHOW DAMAGE AFTER EXPOSURE TO EXTERNAL BUT NOT INTERNAL CIGARETTE-SMOKE

The combination of cigarette smoke and high-level occupational asbesto s exposure produces a synergistic increase in the incidence of lung ca ncer; however, smoking does not affect the incidence of mesothelioma. Here we present the results of tests of two theories that have been pr oposed to explain this phenomenon; namely, that pleural mesothelial ce lls are resistant to cigarette smoke-induced damage and that the pleur al connective tissue acts as a barrier that prevents smoke from reachi ng the mesothelial cells. To test these hypotheses, excised whole rat lung preparations were exposed to either internal (intratracheal) or e xternal (pleural surface) smoke. For comparison, additional excised lu ng preparations were exposed to solutions of hydrogen peroxide either externally or intratracheally. Mesothelial cells exposed to external s moke showed widespread, dose-dependent uptake of Trypan blue. Mesothel ial 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. Ex amination by scanning and transmission electron microscopy showed that internal smoke did not affect mesothelial cell ultrastructure, wherea s external smoke produced obvious mesothelial cell damage and mesothel ial cell detachment. Catalase and deferoxamine, scavengers of active o xygen species, provided protection against smoke-induced mesothelial c ell injury, but inactivated catalase did not. External hydrogen peroxi de produced a very similar, dose-dependent pattern of Trypan blue upta ke and ultrastructural changes. Intratracheal hydrogen peroxide also d amaged mesothelial cells, but the extent of damage was always less tha n with comparable concentrations of external hydrogen peroxide. We con clude that 1) pleural mesothelial cells are sensitive to damage by smo ke-derived active oxygen species; 2) the pattern of injury is similar to that produced by hydrogen peroxide; 3) bronchial epithelial cells a ppear to be less sensitive to smoke-induced oxidant damage than mesoth elial cells; and 4) at least acutely, the pleura appears to act as a b arrier to smoke and penetration of active oxygen species.