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[The role of cycline dependent kinase 4 in the malignant transformation induced by silica].

OBJECTIVE: To study the role of cycline dependent kinase 4 (CDK4) in the malignant transformation of human fetal lung diploid fibroblast cell (2BS) induced by silica. METHODS: Recombination vectors with antisense pXJ41-CDK4 were constructed, and then were transfected into the malignant transformed cells induced by silica. In situ hybridization and immunohistochemistry were used to analyze the expression of CDK4. Cell growth curve, doubling time, cell cycle distribution and the growth capacities on soft agar were analyzed before and after antisense CDK4 RNA was transferred into malignant transformed cells induced by silica. RESULTS: During the malignant transformation of 2BS cells induced by silica, CDK4 gene was overexpressed. Antisense pXJ41-CDK4 transduction suppressed CDK4 gene expression in the antisense pXJ41-CDK4 transfected cells. Antisense CDK4 RNA led to cell cycle arrest, resulting in lengthened G1 phase (the percentages of cells in the G1 phase increased from 45.1% to 58.0%), and eventually attenuated the proliferation of malignant transformed cells induced by silica. At the 8th day, the suppression rates decreased by 77.43%. The doubling time prolonged from 21.0 h to 42.7 h. The growth capacities on soft agar of cells transfected by antisense pXJ41-CDK4 were decreased. CONCLUSION: CDK4 might play an important role in maintaining the transformed phenotype of the cancer cells.

Cell Transformation, Neoplastic↗

Synthesis and crystallization of hybrid spherical colloids composed of polystyrene cores and silica shells.

The Stöber method has been adopted to prepare hybrid core-shell particles by coating the surfaces of monodisperse polystyrene beads with uniform silica shells. Polystyrene beads with diameters in the range of 0.1-1.0 microm have been successfully demonstrated for use with this process, and the thickness of the silica coating could be controlled in the range of 50-150 nm by adjusting the concentration of tetraethoxysilane, the deposition time, or both. The morphology and surface smoothness of the deposited silica were found to strongly depend on a number of parameters such as the surface functional groups on the polymer beads, the pH value of the medium, and the deposition time. Hollow spheres made of silica could be obtained by selectively removing the polymer cores via calcination in air at an elevated temperature or by wet etching with toluene. These core-shell colloids were also explored as building blocks to fabricate long-range ordered lattices (or colloidal crystals) that exhibited stop bands different from those assembled from spherical colloids purely made of either polystyrene or silica.

Journal Article↗

[Biotoxicology and biodynamics of silica nanoparticle].

OBJECTIVE: To investigate the toxicology and biodynamics of silica nanoparticle. METHODS: The silica nanoparticles were injected into mice through tail vein, and the mice were amphimixised, the urine was collected in different time, variations of pathology in organs and tissues of the mice were detected. At the same time, the silica nanoparticles' distribution in the tissues was observed through electron microscope. RESULTS: The silica nanoparticles were detected in all tissues and urine of the mice. The injected mice can reproduce as normal. CONCLUSION: The silica nanoparticles do not have toxicity and can be used in vivo.

Animals↗

Involvement of macrophages in genetic resistance to bone marrow grafts. Studies with two specific antimacrophage agents, carrageenan and silica.

Carrageenans and silica, agents toxic for macrophages, were used in this study to examine the role of macrophages in resistance of irradiated mice to inbred parental and rat bone marrow grafts. Administration of 2.5 mg of carrageenans or 2.5-5 mg of silica particles intravenously to prospective graft recipients resulted in a prompt abrogation of hybrid and xenogeneic resistance. The macrophage stabilizer poly-2-vinylpyridine N-oxide (PVNO) injected subcutaneously in the dose of 150 mg/kg, 24 hr before silica prevented or reduced the suppression of resistance. PVNO, however, did not antagonize the suppression of resistance by carrageenen, horse anti-mouse thymocyte serum and cyclophosphamide. These results suggest that a) a subpopulation is involved in marrow graft rejection by irradiated mice; b) carrageenan and silica apparently act on macrophages by different mechanisms c) horse anti-mouse thymocyte serum and cyclophosphamide may act on cells other than macrophages or they act on macrophages by a different mechanism than silica, to resistance to bone marrow transplantation.

Animals↗

[Experimental silicosis. II. Fibrogenic effect of natural amorphous silica].

Fibrogenic effect of two natural amorphous silica dusts-diatomite from deposits near Leszczawka (Poland) and silica earth (from the USA) was tested on the rats. Pneumoconiosis was produced by intratracheal introduction of 50 mg dust, at a single dose. Fibrogenic effect was assessed after 3, 6 and 9 months after introduction of dust. Analysis of diatomite dust carried out with X-ray diffraction method showed the presence of quartz in a quantity not exceeding 5%, while in silica earth dust from the USA no silica critalline structures were found. Development of fibrogenic changes in lungs of the rats assessed with hydroxyproline (collagen) increase and weight increment of wet lungs was small. The increment of the indices was twice higher as compared with their increment found in the lungs of control animals but lower than in the rats which were given cristalline silica dusts. In histopathological examinations no progressive lung fibrosis was found though some signs of destruction and necrobiosis in some cells were noticed.

Animals↗

Effect of vehicular volume on the early pulmonary injury and inflammatory response in rats inoculated intratracheally with silica.

The effect of vehicular saline solution volume on early lesions induced in rats by intratracheal administration of silica was evaluated. Seventy-two male Long-Evans rats were randomly assigned 6 each to 12 factorial groups (3 X 2 X 2): 3 doses of silica (0, 2.5, and 5 mg), 2 volumes of vehicle (saline solution; 0.1 and 0.5 ml), and 2 postinoculation times (1 and 3 days). Lactate dehydrogenase and alkaline phosphatase activities in the bronchoalveolar lavage fluid supernatant and cell viability of bronchoalveolar cells were used as indicators of cell injury. The number of pulmonary alveolar macrophages and polymorphonuclear leukocytes were used as indicators of inflammatory response. Dose of silica and postinoculation time had a significant (P less than 0.05) effect on the biochemical and cellular composition of lavage fluid. The volume of vehicle in which silica was suspended significantly (P less than 0.05) enhanced the pulmonary injury and inflammatory response. However, dose-volume interaction was only significant (P less than 0.05) in 1 of 6 parameters, indicating that the effect was additive, but not synergistic, in nature. Seemingly, vehicle volume had an enhanced effect on the injury and the inflammatory response induced by intratracheal inoculation of silica.

Animals↗

Formation of granulomas in liver of silica-treated rats.

Hepatic silicosis was induced in rats by an intravenous injection of saline-suspended silica, 40 mg/kg of body weight. Changes in the liver were examined by biochemical, histological and histochemical methods. Infiltration of the liver parenchyma by polymorphonuclear leucocytes was observed only on the first day after silica treatment. Formation of silicotic nodules began on the first day by clustering of liver macrophages. A 22% increase in liver weight and a 67% increase in total liver DNA reflected accumulation of cells in the liver by day 28 after silica injection. Local cell division contributed to this increase. Almost all cells in the nodules contained carbon when the rats had been given ink before silica. Macrophages showed high activity of lysosomal esterases on the first few days after silica treatment; the activity disappeared later. Large granulomas containing hundreds of cells including lymphocytes were seen 226 days after treatment. Hydroxyproline content per gram of liver tissue increased by 35% and 58% by day 80 and 162, respectively. Connective tissue formed capsules around the nodules and grew to their inside. Activities of lysosomal enzymes, beta-D-galactosidase and acid proteases, in serum were increased by 20% and 300%, respectively, 35 days after treatment. Neither malondialdehyde concentration nor superoxide dismutase activity was elevated in silicotic liver.

Animals↗

Use of backscattered electron imaging to quantify the distribution of inhaled crystalline silica.

Inhalation of crystalline silica causes fibrotic pulmonary disease. The lung pathology of silicosis is well characterized and predictable, but the initial patterns of particle deposition and translocation are unknown. Scanning electron microscopy and backscattered electron imaging were utilized to quantify silica particle distribution in the distal air spaces of rats following a three-hour exposure to silica dust at a concentration of 100mg/m3. Lungs were perfused through the vasculature with 2% Karnovsky's fixative at a pressure of 15cm of water for 30 minutes. Blocks of tissue were dissected from five predetermined regions of the left lung and critical point dried. Mounted blocks were further dissected to reveal terminal bronchioles and their attached alveolar ducts. The tissue was sputter-coated with gold. Silica particles were visualized on the alveolar duct surfaces, then counted using negative backscattered electron imaging. The precise area of alveolar duct surfaces was calculated by using a standard magnification of 10,000X and a grid of 64cm2 over the viewing cathode ray tube. Thus, quantitation of silica particles could be expressed as number of particles per square micron. Our data show that there were fewer particles on the alveolar duct surfaces and in alveolar spaces of animals 8 hours after exposure when compared with animals 3 hours post-exposure.

Animals↗

Ultrastructural aspects of the lymphoid follicle-associated cells of the cloacal bursa after treatment with silica or carrageenan.

The present paper describes the ultrastructural changes in the follicle-associated epithelial cells of the cloacal bursae, which were observed after treating chickens with silica or with carrageenan. These substances, which are widely known to be toxic to macrophages, were used to establish whether the behaviour of the follicle-associated epithelial cells is the same as that of the lining epithelial cells, which are not affected by the action of silica and carrageenan, or whether the follicle-associated epithelial cells behave in the same way as macrophages. Experiments showed that silica and carrageenan cause extensive damage to the structure of the follicle-associated epithelial cells. The results, especially those obtained with the endobursal administration of silica, would seem strongly to support the hypothesis that follicle-associated epithelial cells are of mesenchymal origin, because silica is selectively toxic for mesenchymal cells with histiocytic activity.

Animals↗

Effect of a silica-containing etchant on shear bond strength to dentin.

The viscosity of phosphoric acid etchants for enamel and dentin may be increased by the addition of silica. This in vitro study investigated the effect of a silica-containing 10% phosphoric acid gel on the bond strength of composite resin to dentin as compared to a 10% phosphoric acid gel without silica, using 20 extracted human molars. The results indicated that the etchant containing submicron silica provided higher bond strengths than the etchant without a silica constituent. The learning objective of this article is to provide the findings of the study for the clinicians.

Acid Etching, Dental↗

Silica contamination of etched dentin and enamel surfaces: a scanning electron microscopic and bond strength study.

Most acid-etchant gels are thickened with silica, which can leave a particulate residue on dentinal surfaces. Some newer etchants are thickened with polymers, which reportedly leave no surface residue. This study used scanning electron microscopy to examine dentinal and enamel surfaces that had been etched with either silica- or polymer-thickened gels. The silica gels left particulate debris on dentinal surfaces, and this debris was not removed by rinsing with water. There was little evidence of this contaminant on enamel surfaces. Enamel and dentinal surfaces treated with the polymer-thickened gels appeared to be clean and uncontaminated. Shear bond strengths of composite resin to enamel and dentin etched with the different types of gel etchants were also evaluated. Silica contamination did not adversely affect bonding. In fact, etching with silica-thickened gels resulted in slightly higher bond strengths to both substrates. However, the differences were not statistically significant.

Acid Etching, Dental↗

Historical total and respirable silica dust exposure levels in mines and pottery factories in China.

Historical exposure estimates of total dust and respirable silica were made in a recent nested case-referent study of lung cancer among mine and pottery workers in China. Exposure to total dust and respirable silica was assessed in 20 mines and 9 pottery factories. The average total dust concentration was 7.26 mg center dot m-3, with a range from 17.68 mg center dot m-3 in the 1950s to 3.85 mg center dot m-3 in the 1980s, while the average respirable silica dust was 1.22 mg center dot m-3, with a range from 3.89 mg center dot m-3 in the 1950s to 0.43 mg center dot m-3 in the 1980s. The highest respirable silica dust occurred in the underground mining operations (1.43 mg center dot m-3), particularly for manual drillers (9.03 mg center dot m-3). Among all facility types, tungsten mines had the highest respirable silica dust exposure (1.75 mg center dot m-3), while the lowest exposure occurred in copper-iron mines (0.32 mg center dot m-3).

Ceramics↗

[The analysis of peripheral blood lymphocytes of patients with silicosis and effects of silica in vitro].

It is well known that patients with silicosis are frequently associated with hyperglobulinemia, RA or PSS. It is also suggested that silica can drive and activated the immune system. In this study, we intended to measure the percentage of CD4+CD45RA+ cells in the peripheral blood of patients with silicosis and to investigate whether silica can actually activate human lymphocytes in vitro or not. Peripheral blood from 45 patients with silicosis was stained with OKT4 and 2H4 monoclonal antibodies, and measured by FACS analysis at 1st day and also checked similarly after 6 days-incubation without patients' sera. The intracellular Ca++ level was also checked after incubation with the normal human lymphocytes with silica by FACS analysis, using Fluo3-AM. CD4+CD45RA+ T cells decreased significantly in number. One to 5 minutes after the incubation with silica, intracellular Ca++ level increased markedly, which means the activation of lymphocytes in vitro. These results revealed that silica can activate human lymphocytes in vitro, but the role in vivo remains to be clarified.

Aged↗

Laboratory studies on silica induced toxicity and relationship to carcinogenicity.

A review of published laboratory studies was undertaken to provide insight into the biologic basis for silica induced lung toxicity. Experimental animals exhibit markers of silica induced toxicity similar to those exhibited by humans and may also provide a model for resistant populations. Cell culture studies are useful to discern the roles of specific lung cell types and cell mediators in the development of silica induced fibrotic events. The biochemical relationships between silica induced fibrosis and carcinogenesis have not been fully established. Temporal and dose-response relationships for events linking the two endpoints are unknown. Research in this area will provide a more complete understanding of the relationship between the two disease states and hence of the role of silica exposure in human disease.

Air Pollutants, Occupational↗

Noncancer inhalation toxicology of crystalline silica: exposure-response assessment.

Silicosis from inhalation of silica has long been recognized as an occupational hazard. Concern has arisen regarding the potential risk of silicosis from ambient silica (primarily quartz dust). This presentation reviews available data regarding ambient silica levels and estimates of the risk of silicosis at low exposure levels as they relate to the current U.S. Environmental Protection Agency National Ambient Air Quality Standards (NAAQS) for particulate matter. Current data indicate that for individuals not compromised by other respiratory ailments and for ambient environments expected to sustain 10% or less silica fraction in particulate matter with a mean aerodynamic diameter of < or = 10 microns (PM10), maintenance of the 50 micrograms/m3 annual NAAQS for PM10 is adequate to protect against fibrotic effects from ambient silica exposures. Issues such as the large divergence of risk estimates within the occupational setting (particularly at high cumulative exposures) and factors to consider for extrapolating risk in an occupational setting to risk from ambient exposure are discussed.

Air Pollutants↗

The regulation of crystalline silica: an industry perspective.

Silica is ubiquitous in the earth's crust. It occurs in trace to large quantities in rocks and soil. Because it is so common, the regulation of silica has affected a large number of industries, including the mining industry and any industry that uses quartz in the manufacture of a products. Mineral commodities that contain silica include diatomite, bentonite, kaolinite, talc, pyrophyllite, sand and gravel, perlite, pumice, dimension stone, and barite. Products that contain minerals, many of which are associated with silica, include paint, paper, rubber, plastic, pharmaceuticals, food, cement, plaster, cat litter, potting soil, plaster board, and miscellaneous construction materials. In collaboration with some agencies and academic centers, the silica industry is supporting research to lower health risks and to improve the methods of detecting this common material.

Air Pollution↗

Preparation of chiral stationary phase for HPLC based on immobilization of cellulose 3,5-dimethylphenylcarbamate derivatives on silica gel.

The immobilization of cellulose 3,5-dimethylphenylcarbamate derivatives having a polymerizable vinyl group, i.e., 4-vinylphenylcarbamate or 2-methacyloyloxyethylcarbamate, on silica gel was examined under various conditions. The immobilization was basically conducted through the radical copolymerization of the derivatives with a vinyl monomer. Several factors, such as the vinyl monomer content and the type and amount of the vinyl group of cellulose derivatives, were varied. The introduction of a vinyl group onto the silica surface resulted in a more efficient immobilization of the cellulose phenylcarbamate derivatives on the silica gel. As the content of the vinyl group on the cellulose derivatives was reduced, the immobilization became more difficult, although the obtained phase exhibited higher chiral recognition abilities. These immobilized CSPs could be stably used with the eluent containing 10% chloroform, which cannot be used for the phase prepared by coating the derivatives on silica gel. Some racemates were better resolved on the immobilized CSP by using chloroform as a component of the eluent.

Carbamates↗

Immobilization of bacteria in silica matrices using citric acid in the sol-gel process.

The aim of this work was to use citric acid in the sol-gel process to generate an inorganic polymer that allows bacterial survival for long periods of time and to study the influence of different storage temperatures. We compared gram-negative Escherichia coli and gram-positive Staphylococcus aureus, immobilized and preserved at different storage temperatures in silica matrices prepared by the method proposed. Immobilized E. coli and S. aureus in silica matrices were stored in sealed tubes at 20, 4, -20, and -70 degrees C for 4 months during which the number of viable cells was analyzed. Results show that the immobilization in silica matrices using citric acid, to neutralize the alkalinity of the silica precursors, makes the technique not only biocompatible but also easier to perform since polymerization does not occur immediately as it does when hydrochloric acid is utilized.

Biotechnology↗