Abstract
In vitro assays have been used extensively to investigate the toxicity of mineral dusts, including the various forms of crystalline silica. Early in vitro research utilized hemolysis and macrophage cytotoxicity assays to evaluate the membranolytic and cytotoxic effects of silica. These assays were found to have some utility as screens, providing preliminary information on potential in vivo toxicity. In addition, hemolysis and cytotoxicity assays have been useful tools to characterize silica surface functionalities which contribute to its bioactivity. With the recognition that inflammation plays a key role in the pathogenesis of interstitial lung disease, more recent in vitro studies have focused on the ability of silica to activate alveolar macrophages and other lung cells to release oxidants, cytokines, and growth factors. Findings from these studies support the concept that silica-induced secretion of inflammatory proteins such as tumor necrosis factor α are key to the pathogenesis of silicosis. To better understand the potential lung cancer risks associated with silica exposure, in vitro studies have been used to investigate the genotoxic properties of crystalline silica. Crystalline silica is not active in most assays for genotoxic effects; however, direct exposure of DNA to high levels of quartz can result in DNA strand breaks. While this latter observation suggests that silica has the potential to directly damage DNA, there is growing evidence to support a more indirect mechanism for genotoxic effects after silica exposure. For example, in vitro studies have shown that inflammatory cells from silica-exposed rat lungs are mutagenic for alveolar epithelial cells, suggesting that any genotoxic effects of silica exposure may arise secondary to the recruitment and activation of inflammatory cells. In summary, in vitro models have served as useful adjuncts to animal and human studies for delineating mechanisms by which silica interacts with lung cells and tissues to elicit adverse effects. Ultimately, understanding these mechanisms will guide the development of appropriate models for assessing health risks associated with silica exposure. Driscoll, K.E.: The Toxicology of Crystalline Silica Studied In Vitro. Appl. Occup. Environ. Hyg. 10(12):1118–1125; 1995.