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.

Chlorpyrifos (Dursban) is an organophosphate insecticide with extensive domestic and agricultural applications. It is regarded as safe for these purposes; one report of neurotoxicity is attributed to massive ingestion in a suicide attempt. We report eight people who developed peripheral neuropathy after exposure to exterminator-applied commercial Dursban; five also experienced memory loss and cognitive slowing. Evaluation failed to reveal other causes of neurologic dysfunction; symptoms recurred in one patient following accidental reexposure. We conclude that environmental contact with chlorpyrifos can cause sensory neuropathy and CNS dysfunction and that this agent should be used with caution.

Diesel exhaust particles (DEPs) at three concentrations (5, 35, and 50 mg/kg body weight) were instilled into rats intratracheally. We studied gene expression at 1, 7, and 30 days postexposure in cells obtained by bronchoalveolar lavage (BAL) and in lung tissue. Using real-time reverse transcriptase-polymerase chain reaction (RT-PCR), we measured the mRNA levels of eight genes [interleukin (IL)-1β, IL-6, IL-10, iNOS (inducible nitric oxide synthase), MCP-1 (monocyte chemoattractant protein-1), MIP-2 (macrophage inflammatory protein-2), TGF-β1 (transforming growth factor-β1), and TNF-α (tumor necrosis factor-α)] in BAL cells and four genes [IL-6, ICAM-1 (intercellular adhesion molecule-1), GM-CSF (granulocyte/macrophage-colony stimulating factor), and RANTES (regulated upon activation normal T cell expressed and secreted)] in lung tissue. In BAL cells on day 1, high-dose exposure induced a significant up-regulation of IL-1β, iNOS, MCP-1, and MIP-2 but no change in IL-6, IL-10, TGF-β1, and TNF-α mRNA levels. There was no change in the mRNA levels of IL-6, RANTES, ICAM-1, and GM-CSF in lung tissue. Nitric oxide production and levels of MCP-1 and MIP-2 were increased in the 24-hr culture media of alveolar macrophages (AMs) obtained on day 1. IL-6, MCP-1, and MIP-2 levels were also elevated in the BAL fluid. BAL fluid also showed increases in albumin and lactate dehydrogenase. The cellular content in BAL fluid increased at all doses and at all time periods, mainly due to an increase in polymorphonuclear leukocytes. In vitro studies in AMs and cultured lung fibroblasts showed that lung fibroblasts are a significant source of IL-6 and MCP-1 in the lung.

No abstract

Previous studies on symptomatic coal miners have shown that alveolar macrophages, recovered by bronchoalveolar lavage (BAL), release excessive amounts of reactive oxygen species (ROS) and inflammatory cytokines. It has been proposed that these secretions may mediate cell injury and initiate the disease process. We hypothesized that acellular bronchoalveolar lavage fluid (BALF) indices in coal miners chronically exposed to coal dust may reflect the status of important homeostatic modulations in the lung that lead to the development of coal workers' pneumoconiosis (CWP). To test this hypothesis, we measured inflammatory status, oxidant burden, antioxidant defenses, cytokines, growth factors, fibronectin, and alpha(1)-antitrypsin (alpha(1)-AT) in the BALF of healthy never-smoker control subjects, never-smoker underground coal miners with negative radiographs (ILO 0/0-1/0), and two miners with moderate changes in the chest radiographs (ILO 2/2). Interestingly, indices of injury and inflammation increased with the progression of disease in coal miners. Antioxidant enzymes, such as catalase, glutathione peroxidase, and superoxide dismutase, showed a 19-fold, 22-fold, and 6-fold increase above control, respectively, in coal miners with category 2/2 CWP. Significant increases in the secretion of IL-1, IL-6, TNF-alpha, TGF-beta, fibronectin, and alpha(1)-AT also were evident in coal miners with disease. This up-regulation of antioxidant defenses and cytokines was not evident in coal miners in the absence of clinically evident radiographic disease. In addition, the concentration of lipid peroxidation by products in the BALF of coal miners without evidence of radiographic disease showed a moderate 3-fold increase, whereas, in coal miners with category 2/2 CWP it showed a 59-fold increase compared to control subjects. These results are in good agreement with our hypothesis that development of CWP and its progression may be correlated with an oxidative stress and up-regulation of cytokines and mediators of growth.

Fracturing quartz produces silica-based radicals on the fracture planes and generates hydroxyl radicals (OH) in aqueous media. 'OH production has been shown to be directly associated with quartz-induced cell damage and phagocyte activation in vitro. This 'OH production in vitro is inhibited by desferrioxamine mesylate, an Fe chelator, indicating involvement of a Fenton-like reaction. Our objective was to determine if Fe contamination increased the ability of inhaled quartz to cause inflammation and lung injury. Male Fischer 344 rats were exposed 5 hr/day for 10 days to filtered air, 20 mg/m3 freshly milled quartz (57 ppm Fe), or 20 mg/m3 freshly milled quartz contaminated with Fe (430 ppm Fe). High Fe contamination of quartz produced approximately 57% more reactive species in water than quartz with low Fe contamination. Compared to inhalation of quartz with low Fe contamination, high Fe contamination of quartz resulted in increases in the following responses: leukocyte recruitment (537%), lavageable red blood cells (157%), macrophage production of oxygen radicals measured by electron spin resonance or chemiluminescence (32 or 90%, respectively), nitric oxide production by macrophages (71 %), and lipid peroxidation of lung tissue (38%). These results suggest that inhalation of freshly fractured quartz contaminated with trace levels of Fe may be more pathogenic than inhalation of quartz alone. Environ Health Perspect 105(Suppl 5): 1319-1324 (1997)