Potential Role of Silicon-Oxygen Radicals in Acute Lung Injury

"INTRODUCTIONThis paper summarizes our recent investigations of the potential role of silicon-oxygen based free radical species in the biochemical mechanism of the lung injury caused by the inhalation of freshly fractured silica. The impetus for this study came from the following observations. Inhalation of crystalline silica is associated with the development of acute and chronic silicosis. Chronic silicosis is characterized by the development of sharply marked concentric fibrotic nodules in the lung. This occurs over a period of several decades with the development of progressive respiratory impairment. In contrast, acute silicosis is manifested by the filling of the alveoli with an amorphous lipoproteinaceous exudate within a short period after exposure, and rapid development of respiratory disability often leading to fatality. Most studies on the pathogenesis of silicosis have focused on the elucidation of cellular mechanisms of cell injury and the development of chronic silicosis. Because pulmonary responses to crystalline silica are distinctly different for · the acute and chronic silicosis, we hypothesized that the acute response is associated with some unique properties of ·freshly formed silica particle surfaces, due to the formation of some reactive chemical species caused by the rupturing or the silicon-oxygen bonds. In occupations involving drilling, tunneling and sandblasting operations acute silicosis can be correlated with this unique surface reactivity of silica. The formation or reactive species was demonstrated, using electron spin resonance (ESR) spectroscopy (Dalal et al., 1986; Fuibini et al., 1987; Hochstrasser and Antononi, 1972). Grinding of quartz crystals under ultra high vacuum (10-10 torr) leads to the formation of Si- and SiO• radicals and these radicals are quenched by exposure to air and other gases (Hochstrasser and Antonini, 1972). ESR signals have also been reported from micronized quartz samples that were evacuated at 413 K (Bolls et al., 1983). In order to find a more direct relationship of such radicals to acute silicosis, we made ESR measurements on quartz dusts freshly ground in ambient air and found- that indeed grinding under ambient environment leads to the formation of the Si• and SiO• type of radicals which decay on storing the dusts in air or in biological buffers (Dalai et al., 1986; Vallyathan et al., 1988). The Si• and SiO radical formation on grinding has also been reported by Fubini et al. (1987). In addition, we recently found that •OH radicals are generated in aqueous suspensions of freshly ground quartz (Dalai et al., 1988; Shi et al., 1988; Vallyathan et al., 1988). We have subsequently carried out detailed cytotoxicity and biological assays on freshly made as well as aged quartz dusts. As summarized below, the results provide new insight into the biochemical mechanism of acute silicosis."