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Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Silica and ferric oxide are common industrial exposures. Studies have indicated that all commonly occurring forms of crystalline silica can cause fibrotic lung disease. There is evidence to indicate that crystalline silica is carcinogenic in humans who have not developed silicosis, while amorphous silica is not carcinogenic in humans. An important biological response to particles deposited deep in the lung is their engulfment by pulmonary alveolar macrophages (AM). To assess the role of AM in silica-induced lung disease, particle size distribution and surface area of crystalline, gelled, precipitated, and fumed silica, ferric oxide, and aluminum oxide were characterized; the cytotoxicity of the particles to hamster and rat AM in vitro was measured at 0.0-0.5 mg/1 x 10(6) cells at 24 and 48 h using dye exclusion procedures. The count medium diameter for aluminum oxide, ferric oxide, and amorphous silica was equal to or less than 0.38 microns, while for crystalline silica the value was 0.83 microns. The surface areas for the amorphous silicas and the aluminum oxide ranged from 253 to 125 m2/g with gelled silica having the highest value; the values for crystalline silica and ferric oxide were 4.3 and 10.8 m2/g, respectively. Crystalline silica (1.6%) was detected in the fumed silica, while none was detected in precipitated or gelled silica. With gelled silica, based on the dose of the particle, the viability of the hamster AM decreased to 27% at 0.05 mg and to zero at 0.1 mg at 24 h. At doses of 0.05 and 0.1 mg of crystalline, precipitated, or fumed silica, the percent viability decreased significantly to 76-67% and 51-42%, respectively, and to zero at 0.5 mg. Macrophages viable at 24 h decreased further at 48 h compared with the control culture. The ferric oxide and the aluminum oxide showed minimal to no changes in viability. Similar results for the particles were obtained with rat AM. The results indicate that precipitated and fumed amorphous silica tested at equivalent doses are equally as toxic to AM lavaged from two species of rodents as crystalline silica; gelled silica is more toxic than crystalline. Ferric oxide and aluminum oxide are noncytotoxic in this system. The results of this study indicate that the dose as well as the surface area and surface characterization are important determinants in the cytotoxicity of hamster and rat AM to these particles.
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PMID:Influence of particle dose on the cytotoxicity of hamster and rat pulmonary alveolar macrophage in vitro. 805 15

Silica particles cause considerable damage to macrophages resulting in their eventual breakdown. At the same time, the development of silicosis involves a number of mechanisms associated with the activation of macrophages. In suggesting schemes for the pathogenesis of this disease many authors associate the central part with activation, completely neglecting damage to cells. Our experiments have shown, however, that much of the activation phenomena could be reproduced in vitro or in vivo by exposing macrophages to macrophage breakdown products. Alternatively, the secondary character of activation is demonstrated by the fact that it reveals itself only at silica doses which cause part of the cells to lose their viability in the same culture. Our data show that the range of macrophage activation phenomena which could be considered as secondary with respect to the breakdown of cells includes the production of neutrophil attractants, enhanced co-operation with T lymphocytes, increase in phagocytic activity, enhancement of cellular O2 consumption and peroxidation, an increase in the activity of dehydrogenases, reduction in the activity of 5'-nucleotidase, and some other effects. Although not denying that small silica doses may be able to exert a direct activating influence upon the macrophage we do, however, believe that the most important and primary role in the pathogenesis of silicosis is played by the damage to and the breakdown of this cell.
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PMID:On the relationship between activation and breakdown of macrophages in the pathogenesis of silicosis (an overview). 881 62

From West Texas to West Virginia, from California to New York, in industries from oil refining to coal mining and work settings from foundries to shipyards, the United States is experiencing an epidemic of silicosis, a preventable disease. Silica sand has been linked to cancer, and the International Agency for Research on Cancer has named silica as a probable human carcinogen. This article analyzes the reawakening of national concern about silicosis and the social, economic, and epidemiologic factors that have led scientists, policy makers, industrial hygienist, and labor and industry representatives to reassess the danger that silica sand poses to the health of an estimated two million workers in this country.
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PMID:The reawakening of national concern about silicosis. 967 67

Exposure to silica has been associated with progressive pulmonary inflammation and fibrosis. While the fibroblasts play an important role in the pathogenesis of silicosis, the direct interaction between silica and fibroblasts is poorly understood. We observed that silica particles stimulated intracellular ROS generation in Rat2 fibroblast, evidenced by DCFH oxidation. Silica-induced DCFH oxidation was inhibited by catalase and DPI, a flavoenzyme inhibitor. Additionally, the time course of elevation of the intracellular ROS was paralleled by the increases of MEK and ERK phosphorylation. Silica-induced ERK phosphorylation was also effectively attenuated by catalase and DPI. However, SOD enhanced the silica-induced ERK phosphorylation, indicating a role for H(2)O(2) in ERK activation. Furthermore, ERK and MEK phosphorylation are reproduced by H(2)O(2) treatment. Taken together, these results demonstrate that silica stimulates ROS production via flavoenzyme-dependent mechanism in Rat2 fibroblasts and the H(2)O(2), in turn, serves as a signal transduction element in activating MEK-ERK pathway.
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PMID:Silica-induced generation of reactive oxygen species in Rat2 fibroblast: role in activation of mitogen-activated protein kinase. 1047 90

Silica exposure results in an initially acute inflammatory response followed by chronic fibrotic change. The mechanism for the maintenance of silica-induced inflammation has not been understood yet. In silica-induced acute inflammation and chronic fibrosis, various mediators such as reactive oxygen species, cytokines and growth factors are released. And these substances are suggested to have the regulatory role for the inflammation and fibrosis by possessing the potential to influence apoptosis. To demonstrate the apoptosis as an underlying mechanism for the development of silicosis, in vitro and in vivo models were designed. In in vitro study, we evaluated that apoptotic cell fraction in silica (10, 50 microg/cm2)-treated A549 cells was significantly increased in comparison with control by FACS (fluorescein activated cell sorter). Also genomic DNA from silica (10, 50 microg/cm2)-treated A549 showed DNA ladder formation while control and 1 microg/cm2 groups didn't. In in vivo study, total cell numbers and apoptotic cell numbers of BAL (bronchoalveolar lavage) fluid from silica (10, 20, 40 mg/kg)-instilled rats were significantly higher than control group from 1 week. From these results, we concluded acute and chronic presence of apoptosis may contributes to silica-induced acute inflammation and chronic fibrosis.
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PMID:Silica-induced apoptosis in vitro and in vivo. 1051 Dec 80

By measuring the activity of telomerase in a silica-instilled rat lung, the study found a significant increase in telomerase activity compared to that of the control. Pneumoconiosis displays the characteristics of fibroblast-proliferation and accumulation of collagen, which finally causes the pathologic changes of irreversible and progressive fibrosis of the lung. On the basis of the hypothesis that cellular proliferation may trigger telomerase-activity, the experiment was carried out with telomerase-activation in silicosis. Silica-instilled rat lungs showed increased activity of telomerase, which was measured by TRAP (telomeric repeat amplification protocol) assay, at the time of the 1st, 5th and 8th week after intratracheal instillation of silica in vivo. However, no activity was shown in silica-co-cultured fibroblast in vitro. By summarizing these results, the activity of telomerase is thought to be a very sensitive marker for the evaluation of pathogenicity, showing cellular immortalization in an experimental silicosis model.
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PMID:Activation of telomerase by silica in rat lung. 1064 71

Silicosis is a serious occupational lung disease associated with irreversible pulmonary fibrosis. The interaction between inhaled crystalline silica and the alveolar macrophage (AM) is thought to be a key event in the development of silicosis and fibrosis. Silica can cause direct injury to AMs and can induce AMs to release various inflammatory mediators. Acute silicosis is also characterized by a marked elevation in surfactant apoprotein A (SP-A); however, the role of SP-A in silicosis is unknown. We investigated whether SP-A directly affects the response of AMs to silica. In this study, the degree of silica toxicity to cultured rat AMs as assessed by a (51)Cr cytotoxicity assay was shown to be dependent on the time of exposure and the concentration and size of the silica particles. Silica directly injured rat AMs as evidenced by a cytotoxic index of 32.9 +/- 2.5, whereas the addition of rat SP-A (5 microg/ml) significantly reduced the cytotoxic index to 16.6 +/- 1.2 (P < 0. 001). This effect was reversed when SP-A was incubated with either polyclonal rabbit anti-rat SP-A antibody or D-mannose. These data indicate that SP-A mitigates the effect of silica on AM viability, and this effect may involve the carbohydrate recognition domain of SP-A. The elevation of SP-A in acute silicosis may serve as a normal host response to prevent lung cell injury after exposure to silica.
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PMID:Surfactant protein A prevents silica-mediated toxicity to rat alveolar macrophages. 1074 48

An accelerated silicosis case made our Occupational Health Unit focus on a pathology thought dropping so far to die out. Furthermore this event occurred in a manufacturing (lost-wax process in jewelry casting) regarded as a low-risk exposure. Besides unsuitable procedures, the user had underestimated the specific risk of that raw material (talcum-like powder at 60-80% silica crystalline level), commonly called "gypsum", inappropriately labelled since not yet adequately classified by the hazardous substances list. The widespreading of this manufacture in our area (Vicenza district) and the recent inclusion of Silica Crystalline in the Class 1 made by IARC (Jan 1997) have urged this Unit to take action in industrial hygiene investigations, instructions to the workers, mandatory directions to dealers concerning the proper hazard labelling for products containing silica crystalline and circulation of information among other Occupational Health Units involved.
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PMID:[Acute silicosis in jewelry casting]. 1077 39

Nuclear factor-kappaB (NF-kappaB) is a multiprotein complex that may regulate a variety of inflammatory cytokines involved in the initiation and progression of silicosis. The present study documents the ability of in vitro silica exposure to induce DNA-binding activity of NF-kappaB in a mouse peritoneal macrophage cell line (RAW264.7 cells) and investigates the role of reactive oxygen species (ROS) and/or protein tyrosine kinase in this activation. In vitro exposure of mouse macrophages to silica (100 microg/ml) resulted in a twofold increase in ROS production, measured as the generation of chemiluminescence (CL), and caused activation of NF-kappaB. Silica-induced CL was inhibited 100% by superoxide dismutase (SOD) and 75% by catalase, while NF-kappaB activation was inhibited by a variety of antioxidants (catalase, superoxide dismutase, alpha-tocopherol, pyrrolidine dithiocarbamate, or N-acetylcysteine). Further evidence for the involvement of ROS in NF-kappaB activation is that 1 mM H2O2 enhanced NF-kappaB/DNA binding and that this activation was inhibited by catalase. Specific inhibitors of protein tyrosine kinase, such as herbimycin A, genistein, and AG-494, prevented NF-kappaB activation in silica-treated cells. Genistein and AG-494 also reduced NF-kappaB activation in H2O2-treated cells. Results confirm that tyrosine phosphorylation of several cellular proteins (approximate molecular mass of 39, 58-70, and 103 kD) was increased in silica-exposed macrophages and that genistein inhibited this silica-induced phosphorylation. In contrast, inhibitors of protein kinase A or C, such as H89, staurosporin, calphostin C, and H7, had no marked inhibitory effect on silica-induced NF-kappaB activation. The results suggest that ROS may play a role in silica-induced NF-kappaB activation in macrophages and that phosphorylation events mediated by tyrosine kinase may be involved in this activation.
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PMID:Silica-induced nuclear factor-kappaB activation: involvement of reactive oxygen species and protein tyrosine kinase activation. 1083 16

The relationship between crystalline silica and lung cancer has been the subject of many recent publications, conferences, and regulatory considerations. An influential, international body has determined that there was sufficient evidence to conclude that quartz and cristobalite are carcinogenic in humans. The present authors believe that the results of these studies are inconsistent and, when positive, only weakly positive. Other, methodologically strong, negative studies have not been considered, and several studies viewed as providing evidence supporting the carcinogenicity of silica have significant methodological weaknesses. Silica is not directly genotoxic and is a pulmonary carcinogen only in the rat, a species that seems to be inappropriate for assessing particulate carcinogenesis in humans. Data on humans demonstrate a lack of association between lung cancer and exposure to crystalline silica. Exposure-response relationships have generally not been found. Studies in which silicotic patients were not identified from compensation registries and in which enumeration was complete did not support a causal association between silicosis and lung cancer, which further argues against the carcinogenicity of crystalline silica.
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PMID:Silica, silicosis, and lung cancer: a response to a recent working group report. 1128 67


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