Abstract
Some crystalline silicas cause pulmonary fibrosis and tumors in rats. Work from our laboratory and others has focused on whether these lesions reflect unique or similar responses of lung fibroblasts and epithelial cells to silica in comparison to a number of insoluble particles (e.g., carbon black, shale, titanium dioxide, etc.) also associated with fibrotic and carcinogenic responses in rat inhalation models. Inhalation of asbestos and silica, as well as nuisance dusts at overload concentrations, also causes marked and prolonged inflammation in the lung. The elaboration of active oxygen species and other inflammatory mediators by these minerals may be intrinsic to the disease process. Elevated and protracted induction of genes encoding antioxidant enzymes is observed after inhalation of asbestos or cristobalite silica. These studies indicate that cells of the lung respond defensively to inflammatory particles. Oxidant stress can be important to the development of genotoxicity, cell proliferation, and necrosis. Since cell proliferation is a key component of pulmonary fibrosis and tumor promotion, we are currently focusing on early response protooncogenes and transcription factors which may be induced in both rat lung fibroblasts and epithelial cells after exposure to asbestos and silica. An important aspect of this work is whether active oxygen species are important in cell signaling pathways by these minerals. Studies to elucidate the mechanisms of action of silica at the cellular and molecular levels are necessary to determine whether there is a threshold of response to silica. Mossman, B.T.; Jimenez, L.A.; Bérubé, K.; Quinlan, T.; Janssen, Y.M.W.: Possible Mechanisms of Crystalline Silica-Induced Lung Disease. Appl. Occup. Environ. Hyg. 10(12):1115–1117; 1995.
