Exposure to asbestos and silica is associated with a variety of pulmonary disorders including pulmonary interstitial fibrosis. Although asbestosis and silicosis have been recognized as occupational lung diseases for nearly a century, the mechanism(s) by which these fibrogenic minerals induce lung cell injury and fibrosis is speculative, particularly at the cellular level. In this proposal we hypothesize that oxygen free radicals may be one important mediator of lung cell damage and/or fibrosis in vitro and in vivo after exposure to fibrogenic minerals. To test the hypothesis, we will undertake the following studies: 1. Cytotoxicity induced by exposure in vitro to various concentrations of asbestos fibers and silicon dioxides will be determined in lung fibroblasts, alveolar macrophages and epithelial cells. 2. Production of superoxide radical, hydrogen peroxide (H2O2), and the hydroxyl radical (OH.) by these cells after exposure to minerals at various concentrations will be monitored and correlated with results of #1 above. 3. Levels of superoxide dismutase (SOD) in lung fibroblasts, alveolar macrophages and epithelial cells after exposure to minerals in vitro and in lung sections of rats after inhalation of asbestos in vivo will be measured using quantitative biochemical assays and immunocytochemical techniques. 4. We will determine whether mineral-induced injury to alveolar macrophages, fibroblasts and epithelial cells in vitro can be prevented by the addition of scavengers of superoxide and hydroxyl radicals; These studies will be important in elucidating the importance of oxygen free radicals in mineral-induced lung cell injury, asbestosis and silicosis. In addition, they will contribute information on possible preventative and therapeutic approaches to these serious occupational diseases.
