RESUMEN
An in vitro plasmid assay was employed to study the bioreactivity of PM (particulate matter) in Beijing air. It was found that the TD20 (toxic dose of PM causing 20% of plasmid DNA damage) of Beijing PM can be as low as 28 microg ml(-1) and as high as >1000 microg ml(-1). Comparison of the physical properties, such as morphology and size distribution, and oxidative potential indicates that the PM(2.5) (particulate matter with an aerodynamic diameter of 2.5 microm or less) has a stronger oxidative capacity than PM(10) (particulate matter with an aerodynamic diameter of 10 microm or less), and that the higher number percentages of soot aggregates and lower number percentages of mineral and fly ashes are associated with the higher oxidative capacity. Although the mass of PM(10) during dust storms is commonly 5 times higher than that during non-dust storm episodes, the oxidative capacity of PM(10)s of dust storms is much lower than that of the non-dust storm PM(10)s. The water-soluble fractions and intact whole particle solutions of Beijing airborne particles produce similar plasmid assay results, demonstrating that the bioreactivity of Beijing airborne particles is mainly sourced from the water-soluble fraction. In the samples with stronger bioreactivity, the total analyzed water soluble Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As and Pb (ppm) concentrations are higher. The water soluble zinc shows a good negative correlation with TD20s, suggesting that the water-soluble zinc is probably the major element responsible for the plasmid DNA damage.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Daño del ADN , ADN/efectos de los fármacos , Monitoreo del Ambiente/métodos , Plásmidos/química , Contaminantes Atmosféricos/química , China , Espectrometría de Masas , Microscopía Electrónica de Transmisión , Tamaño de la Partícula , SolubilidadRESUMEN
People spend the majority of their time indoors mostly in the domestic environment, where their health may be effected by significant airborne particulate pollution. The indoor/outdoor air quality at six homes in Wales and Cornwall was investigated, based on different locations (urban, suburban, rural) and household characteristics (smokers, non-smokers). The spatial and temporal variations in PM10 mass were monitored for a calendar year, including ambient weather conditions. The activities of individuals within a household were also recorded. Monitoring of PM10 took place inside (kitchen, living room, bedroom) homes, along with concomitant collections outdoors. Samples were subjected to gravimetric analysis to determine PM10 concentrations and examined by scanning electron microscopy to identify the types of particles present on the filters. The results of the study show there are greater masses of PM10 indoors, and that the composition of the indoor PM10 is controlled by outdoor sources, and to a lesser extent by indoor anthropogenic activities, except in the presence of tobacco smokers. The indoor and outdoor PM10 collected was characterised as being a heterogeneous mixture of particles (soot, fibres, sea salt, smelter, gypsum, pollen and fungal spores).
Asunto(s)
Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Exposición a Riesgos Ambientales , Actividades Cotidianas , Sulfato de Calcio/análisis , Carbono/análisis , Inglaterra , Monitoreo del Ambiente , Humanos , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Polen , Esporas , Contaminación por Humo de Tabaco/análisis , GalesRESUMEN
BACKGROUND: The Soufriere Hills, a stratovolcano on Montserrat, started erupting in July 1995, producing volcanic ash, both from dome collapse pyroclastic flows and phreatic explosions. The eruptions/ash resuspension result in high concentrations of suspended particulate matter in the atmosphere, which includes cristobalite, a mineral implicated in respiratory disorders. AIMS: To conduct toxicological studies on characterised samples of ash, together with major components of the dust mixture (anorthite, cristobalite), and a bioreactive mineral control (DQ12 quartz). METHODS: Rats were challenged with a single mass (1 mg) dose of particles via intratracheal instillation and groups sacrificed at one, three, and nine weeks. Acute bioreactivity of the particles was assessed by increases in lung permeability and inflammation, changes in epithelial cell markers, and increase in the size of bronchothoracic lymph nodes. RESULTS: Data indicated that respirable ash derived from pyroclastic flows (20.1% cristobalite) or phreatic explosion (8.6% cristobalite) had minimal bioreactivity in the lung. Anorthite showed low bioreactivity, in contrast to pure cristobalite, which showed progressive increases in lung damage. CONCLUSION: Results suggests that either the percentage mass of cristobalite particles present in Montserrat ash was not sufficient as a catalyst in the lung environment, or its surface reactivity was masked by the non-reactive volcanic glass components during the process of ash formation.
Asunto(s)
Silicatos de Aluminio/toxicidad , Polvo/efectos adversos , Pulmón , Dióxido de Silicio/toxicidad , Erupciones Volcánicas/efectos adversos , Animales , Líquido del Lavado Bronquioalveolar/citología , Células Epiteliales/efectos de los fármacos , Pulmón/patología , Masculino , Minerales/análisis , Tamaño de los Órganos/efectos de los fármacos , Surfactantes Pulmonares/metabolismo , Ratas , Ratas Sprague-Dawley , Indias OccidentalesRESUMEN
Based on monitoring data, the daily and day-to-day changes of PM10 mass concentrations in northwestern Beijing urban area during heating-period were discussed. XRD and SEM were applied to study the mineral compositions and morphology of the PM10, respectively. It was concluded that concentration of PM10 at nighttime was higher than that at daytime generally. By XRD analysis, it was found that the finer the particles, the less the minerals in it. Furthermore, from the SEM micrograph, five types of the particles, mostly from coal burning and diesel exhaust in number concentration, were classified as chain-like aggregate, cluster aggregate, spherical particle, flake-like particle and non-regular particle.
Asunto(s)
Contaminantes Atmosféricos/química , Carbón Mineral , Emisiones de Vehículos , Contaminantes Atmosféricos/clasificación , Calefacción , Microscopía Electrónica de Rastreo/métodos , Tamaño de la Partícula , Periodicidad , Difracción de Rayos X/métodosRESUMEN
Oxidative stress may be a fundamental mode of injury associated with inspired particles. To examine this, we determined the ability of three carbon black particles (CBPs; M120, M880, and R250) and two forms of silicon dioxide, amorphous (Cabosil) and crystalline (DQ12) quartz, to deplete epithelium lining fluid antioxidant defenses. Single and composite antioxidant solutions of uric acid, ascorbic acid (AA), and reduced glutathione (GSH) were examined in the presence of particle concentrations of 150 microgram/ml. Uric acid was not depleted by any particle considered. AA was depleted in a near-linear fashion with time by the three different CBPs; however, AA depletion rates varied markedly with CBP type and decreased in the presence of metal chelators. An initially high GSH depletion rate was noted with all CBPs, and this was always accompanied by the appearance of oxidized glutathione. Exposure to Cabosil or DQ12 did not result in the loss of GSH. Together, these data demonstrate that particle type, size, and surface area are all important factors when considering particle-antioxidant interactions in the airways.
Asunto(s)
Contaminantes Atmosféricos/farmacología , Antioxidantes/metabolismo , Líquidos Corporales/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Ácido Ascórbico/metabolismo , Carbono/farmacología , Interacciones Farmacológicas , Epitelio/metabolismo , Glutatión/metabolismo , Disulfuro de Glutatión/biosíntesis , Dióxido de Silicio/farmacología , Soluciones , Ácido Úrico/metabolismoRESUMEN
OBJECTIVES: To begin to elucidate the mechanisms of particle toxicity to the lung, the bioreactivity of four carbon black (CB) and diesel exhaust particles ((DEPs), a surrogate for particulate matter of aerodynamic diameter < 10 microns (PM10), were examined with primary cultures of Clara and type II epithelial cells. METHODS: The particles were extensively characterised by surface chemistry, size, and aggregation properties. Toxicity of the particles was assessed by determining cell attachment to an extracellular matrix substratum. RESULTS: The spherulite size range for the particles ranged from 50, 40, 20, 20, and 30 nm for CB1-4 and DEPs. All particle samples had different surface chemical compositions. CB1 was the least toxic to Clara (170 micrograms) and type II cells (150 micrograms) and CB4 was the most toxic (55 micrograms and 23 micrograms respectively). DEPs stored for 2 weeks were equally toxic to both epithelial cell types (27-28 micrograms). DEPs became progressively less toxic to type II cells with time of storage. Both primary epithelial cell types internalised the particles in culture. CONCLUSIONS: Bioreactivity was found to be related to CB particle spherulite size and hence surface area: the smaller the particle and larger the surface area, the more toxic the particles. Also, CB particles with the most complicated surface chemistry were the most bioreactive. Freshly prepared DEPs were equally toxic to type II and Clara cells and they became progressively less toxic to the type II cells with time. With all CB and DEPs, the primary epithelial cells internalised the particles, although this was noted most in cells of low functional competence.
Asunto(s)
Carbono/toxicidad , Células Epiteliales/efectos de los fármacos , Emisiones de Vehículos/toxicidad , Animales , Células Cultivadas/efectos de los fármacos , Humanos , Ratones , Tamaño de la PartículaRESUMEN
To evaluate the contribution of reactive nitrogen species to inflammation by asbestos, Fischer 344 rats were exposed to crocidolite or chrysotile asbestos by inhalation to determine whether increases occurred in nitric oxide (NO.) metabolites from alveolar macrophages (AMs). AMs from animals inhaling asbestos showed significant elevations (p < .05) in nitrite/nitrate levels which were ameliorated by NG-monomethyl-L-arginine (NMMA), an inhibitor of inducible nitric oxide synthase (iNOS) activity. Temporal patterns of NO. generation from AMs correlated with neutrophil influx in bronchoalveolar lavage samples after asbestos inhalation or bleomycin instillation, another model of pulmonary fibrosis. To determine the molecular mechanisms and specificity of iNOS promoter activation by asbestos, RAW 264.7 cells, a murine macrophage-like line, and AMs isolated from control rats were exposed to crocidolite asbestos in vitro. These cells showed increases in steady-state levels of iNOS mRNA in response to asbestos and more dramatic increases in both iNOS mRNA and immunoreactive protein after addition of lipopolysaccharide (LPS). After transfection of an iNOS promoter/luciferase reporter construct, RAW 264.7 cells exposed to LPS, crocidolite asbestos and its nonfibrous analog, riebeckite, revealed increases in luciferase activity whereas cristobalite silica had no effects. Studies suggest that NO. generation may be important in cell injury and inflammation by asbestos.
Asunto(s)
Amianto/toxicidad , Macrófagos Alveolares/efectos de los fármacos , Nitratos/metabolismo , Óxido Nítrico/biosíntesis , Nitritos/metabolismo , Administración por Inhalación , Animales , Bleomicina/farmacología , Líquido del Lavado Bronquioalveolar/citología , Células Cultivadas , Radicales Libres , Inmunohistoquímica , Macrófagos Alveolares/metabolismo , Masculino , Oxidación-Reducción , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/metabolismo , Ratas , Ratas Endogámicas F344RESUMEN
Diesel particles form a large component of the fine particle fraction (PM10) in urban air in the UK. During pollution episodes small increases in PM10 have been linked to detrimental health effects. The comparative toxicological effects of diesel exhaust and other well-characterised particles (carbon black, amorphous and crystalline silica) on rat respiratory epithelium were investigated in the present study. The effects of small masses of particles (1 mg) delivered by intratracheal instillation were monitored by changes in components of lavage fluid. Respirable, crystalline quartz, produced significant increases in lung permeability, persistent surface inflammation, progressive increases in pulmonary surfactant and activities of epithelial marker enzymes up to 12 weeks after primary exposure. Ultrafine amorphous silica did not induce progressive effects but it promoted initial epithelial damage with permeability changes and these regressed with time after exposure. By contrast, ultrafine/fine carbon black had little, if any, effect on lung permeability, epithelial markers or inflammation, despite being given at a dose which readily translocated the epithelium and which has been reported to induce inflammation. Similarly, diesel exhaust particles produced only minimal changes in lavage components, although they were smaller individual particles and differed in surface chemistry from carbon black. It is concluded that diesel exhaust particles are less damaging to respiratory epithelium than silicon dioxide and that the surface chemistry of a particle is more important than ultrafine size in explaining its biological reactivity.
Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Carbono/efectos adversos , Pulmón/efectos de los fármacos , Animales , Biomarcadores , Carbono/farmacología , Permeabilidad de la Membrana Celular/efectos de los fármacos , Epitelio/efectos de los fármacos , Epitelio/fisiología , Inflamación/inducido químicamente , Pulmón/fisiología , Masculino , Neutrófilos/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Tensoactivos/metabolismoRESUMEN
Asbestos causes protracted, dose-dependent increases in steady-state mRNA levels of the proto-oncogenes c-fos and c-jun, and AP-1 DNA-binding activity in normal rat pleural mesothelial (RPM) cells (1). To determine the phenotypic end points of overexpression of these early response genes by asbestos, both cell proliferation and apoptosis were examined in confluent RPM cells exposed to a range of concentrations (1.25 to 10 micrograms/cm2 dish) of crocidolite asbestos for 24 and 48 h. Quantitation of RPM cells pulsed with 5-bromo-2'-deoxyuridine revealed that asbestos caused dose-dependent decreases in cells undergoing DNA synthesis. Decreases in cell proliferation were accompanied by dose-related increases in apoptosis using (1) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (i.e., ApopTag technique), (2) 4',6-diamidino-2-phenylindole cell staining, and (3) fluorescent-activated cell sorter after incorporation of propidium iodide. Less striking but significant dose-related increases in apoptosis were observed in RPM cells exposed to H2O2 (300 microM), and no apoptosis was seen after exposure of cells to high concentrations (10 micrograms/cm2 dish) of glass beads. Our results are unique in that they demonstrate that asbestos induces apoptosis in mesothelial cells at concentrations eliciting increased expression of the proto-oncogenes c-fos and c-jun.
Asunto(s)
Apoptosis/efectos de los fármacos , Asbesto Crocidolita/farmacología , Células Epiteliales , Animales , Bromodesoxiuridina/metabolismo , Colorantes , ADN/análisis , ADN/biosíntesis , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Hibridación Fluorescente in Situ , Indoles , Pleura/citología , Propidio , Ratas , Inhibidores de Serina ProteinasaRESUMEN
Patterns of cell proliferation in lung and pleura and development of histopathologic lesions were studied in lungs from Fischer 344 rats after inhalation exposure to chrysotile or crocidolite asbestos at average airborne concentrations of approximately 8 mg/m3 air for 5 and 20 days and after 20 days of exposure followed by an additional 20 days in room air (20 + 20 days). To assess cell proliferation rats were injected with 5-bromo-2'-deoxyuridine (BrdU) at various time points after initiation of exposure to asbestos. Image analysis was used to quantitate the effects of chrysotile and crocidolite on BrdU labeling indices in the following lung compartments: (1) interstitium, (2) alveolar duct region, (3) bronchial epithelium, and (4) visceral mesothelium. With the exception of mesothelium, which exhibited significant increases in BrdU incorporation in rats exposed to crocidolite at 20 + 20 days, asbestos-induced elevations in BrdU uptake in other compartments were transient with labeling comparable to sham controls at later time points. Histopathology of rat lungs revealed fibrotic lesions of a greater extent and severity at 20 days in rats exposed to crocidolite, but fibrosis occurred in both asbestos-exposed groups after an additional 20 days in clean air (20 + 20). Quantification of fiber burden in rat lung after inhalation of comparable airborne concentrations of either fiber type demonstrated that inhalation of crocidolite asbestos led to a higher fiber retention when compared to chrysotile asbestos. Our results indicate that chrysotile and crocidolite asbestos induce different patterns of cell proliferation in lung and pleural cells. The protracted increases in BrdU labeling of mesothelial cells by crocidolite may reflect increased retention of fibers and/or inherent differences between types of asbestos.
Asunto(s)
Asbesto Crocidolita/toxicidad , Asbestos Serpentinas/toxicidad , Pulmón/efectos de los fármacos , Administración por Inhalación , Animales , Asbesto Crocidolita/administración & dosificación , Asbesto Crocidolita/análisis , Asbestos Serpentinas/administración & dosificación , Asbestos Serpentinas/análisis , Bromodesoxiuridina/metabolismo , División Celular/efectos de los fármacos , Células Epiteliales , Epitelio/efectos de los fármacos , Epitelio/patología , Procesamiento de Imagen Asistido por Computador , Técnicas para Inmunoenzimas , Pulmón/química , Pulmón/citología , Pulmón/patología , Masculino , Fibras Minerales/análisis , Ratas , Ratas Endogámicas F344 , Pruebas de ToxicidadRESUMEN
Biochemical and molecular markers of inflammation, cell proliferation, and pulmonary fibrosis were studied in lungs and bronchoalveolar lavage preparations from Fischer 344 rats at time periods from 3 to 20 days after inhalation of two airborne concentrations (0.18 and 8.2 mg/m3 air) of chrysotile asbestos. Additional groups of animals were examined for lung histopathology and cell proliferation with an antibody to 5-bromo-2'-deoxyuridine after exposure to asbestos for 5 and 20 days and after 20 days of exposure followed by an additional 20 days in room air. Exposure to chrysotile at the higher concentration caused protracted increases in steady-state mRNA levels of manganese-containing superoxide dismutase and elevation in glyceraldehyde-3-phosphate dehydrogenase mRNA at 3 days, but levels of mRNAs encoding copper-zinc-containing superoxide dismutase, ornithine decarboxylase, and the proto-oncogene, c-jun were not statistically elevated from levels occurring in lung homogenates from sham control rats. Differential cell counts in bronchoalveolar lavage revealed an early infiltration of neutrophils that correlated with focal areas of increased cellularity and fibrosis in rat lungs at the higher concentrations of asbestos. However, elevations in lung hydroxyproline were not observed. Significant increases in epithelial cells of the bronchi, the interstitial compartment of the lung, and mesothelial cells incorporating 5-bromo-2'-deoxyuridine, an indication of DNA synthesis, were noted in the higher chrysotile group at 5 days, but labeling in all cell compartments was comparable with that occurring in sham controls at later time points. Indicators of inflammation, increased cell proliferation, and pulmonary fibrosis were not observed in the lungs of rats exposed to the lower concentration of chrysotile. Thus, results indicate that cellular and molecular markers of inflammation and proliferation in lung are dose-related and indicative of the histopathological development of asbestosis.