Silicosis is a devastating pulmonary disease that continues to occur in industrial workplaces. Its pathogenesis is under critical evaluation, and this report provides new concepts on the possible early events that occur in lungs resulting from the inhalation of freshly fractured versus aged quartz in the development of two diverse disease entities. In this study, we evaluated the biochemical and pathologic changes in the lavagate and lungs of rats exposed to freshly fractured quartz (generated by jet milling), aged quartz (milled then aged for 2 mo prior to use), or clean air 5 h a day for 10 d over a 2-wk period. The concentration of crystalline quartz in the chambers averaged 20 mg/m3. Particle concentrations and particle size were similar for the freshly milled and aged quartz exposures. However, free radical concentrations associated with the freshly milled quartz samples were significantly higher than those for aged quartz. After a 2-wk exposure, animals were killed and studied by bronchoalveolar lavage and pulmonary histopathology. Inhalation of aged quartz increased the number of bronchoalveolar lavage cells, demonstrated histopathologic evidence of increased pulmonary infiltrates, showed enhanced concentrations of biochemical markers of lung injury, increased lipid peroxidation, and the ability of pulmonary phagocytes to produce more oxygen radicals. In general, all these pulmonary responses were significantly more pronounced after inhalation of freshly fractured quartz compared with aged quartz. In contrast, antioxidant enzymes showed decreased concentrations in the freshly fractured quartz-exposed group compared with the aged quartz-exposed animals.(ABSTRACT TRUNCATED AT 250 WORDS)

These results document that exposure to welding can cause changes in serum biomarkers of oxidative stress that may be valuable in clinical monitoring of disease development and in assessing whether further reduction of worker exposures is needed.

In previous reports from this study, measurements of pulmonary inflammation, bronchoalveolar lavage cell cytokine production and nuclear factor-kappa B activation, cytotoxic damage, and fibrosis were detailed. In this study, we investigated the temporal relationship between silica inhalation, nitric oxide (NO), and reactive oxygen species (ROS) production, and damage mediated by these radicals in the rat. Rats were exposed to a silica aerosol (15 mg/m(3) silica, 6 h/day, 5 days/wk) for 116 days. We report time-dependent changes in 1) activation of alveolar macrophages and concomitant production of NO and ROS, 2) immunohistochemical localization of inducible NO synthase and the NO-induced damage product nitrotyrosine, 3) bronchoalveolar lavage fluid NO(x) and superoxide dismutase concentrations, and 4) lung lipid peroxidation levels. The major observations made in this study are as follows: 1) NO and ROS production and resultant damage increased during silica exposure, and 2) the sites of inducible NO synthase activation and NO-mediated damage are associated anatomically with pathological lesions in the lungs.