Alteration of superoxide dismutase activity in tracheal epithelial cells by asbestos and inhibition of cytotoxicity by antioxidants.
We report here the inhibition of asbestos-induced cytotoxicity in a hamster tracheal epithelial cell line by superoxide dismutase, a scavenger of superoxide (O2-.), and by mannitol and dimethylthiourea, scavengers of the hydroxyl radical (OH.). By using these agents, cell damage was ameliorated in cultures exposed to long (greater than 10 microns in length) fibers of chrysotile and crocidolite asbestos. In contrast, injury to epithelial cells by short (less than or equal to 2 microns) chrysotile or glass fibers was not prevented by scavengers of O2-., OH., H2O2 or 1O2 (singlet oxygen). These results implicate active oxygen species as mediators of injury by long asbestos fibers to cells of the respiratory tract. By using immunocytochemical and biochemical techniques, we detected appreciable amounts of copper-zinc superoxide dismutase in hamster tracheobronchial epithelial cells and alveolar macrophages in vitro and in histologic sections of rat and human respiratory tract. Activity of total endogenous superoxide dismutase (copper-zinc and manganese forms) increased in tracheal epithelial cells exposed for several days in vitro to either crocidolite or chrysotile asbestos but was unchanged in untreated cells and those exposed to comparable amounts of glass fibers. After inhalation of asbestos by rats, or exposure of cells in culture to asbestos, long fibers were observed protruding from both epithelial cells and alveolar macrophages. The unsuccessful phagocytosis of long fibers of asbestos coupled with generation of oxygen free radicals might explain the increased pathogenic potential of long fibers in asbestos-associated diseases of the respiratory tract.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001194:Asbestos / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002999:Clone Cells; D006224:Cricetinae; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D005609:Free Radicals; D006651:Histocytochemistry; D007120:Immunochemistry; D008854:Microscopy, Electron; D008903:Minerals / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D011868:Radioisotopes; D012643:Selenium / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
D000975:Antioxidants; D005609:Free Radicals; D008903:Minerals; D011868:Radioisotopes; D001194:Asbestos; D013482:Superoxide Dismutase; D012643:Selenium; D010100:Oxygen