OPPT_Asbestos, Part I: Chrysotile_Supplemental Search

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2979

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OPPT REs

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Sept. 21, 2020, 6:27 a.m.

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Journal Article

Abstract  The extent of airborne release of fibers from asbestos substitute materials used in high friction products was evaluated. Dust was collected after rubbing brake and clutch linings containing man made mineral fibers and Kevlar with emery paper. Four air samples were collected and examined by transmission electron microscopy (TEM) and energy dispersive X-ray analysis. At x3000, TEM examination showed Kevlar fibers in the respirable range which were capable of deep penetration into the lungs. Of the fibers, 96% had diameters below 2.5 microns and all were more than 80 microns in length. Significant amounts of dust were produced by the clutch plates; samples included carbon (7440440) and inorganic fibers of silicon (7440213) (Si), aluminum (7429905) (Al), calcium-sulfate (7778189), and calcium (7440702) (Ca), as well as some metallic fibers like copper (7440508). The truck brake shoes for trucks had inorganic fibers containing Si, Ca, Al, sulfur (7704349), magnesium (7439954), sodium (7440235), and a small amount of chrysotile (12001295) was also found, while Kevlar was not detected. The majority of car brake shoe fibers were glass. The authors conclude that replacement fibers generate substantially fewer fibers than asbestos, but that the size and inertness of Kevlar fibers may indicate the potential for pulmonary retention.

Journal Article

Abstract  Induction of matrix metalloproteinase, tissue inhibitors of metalloproteinase, and extracellular matrix mRNA expression by mineral fibers and cigarette smoke was studied in rats. Male Wistar-rats were instilled intratracheally with 2 milligrams of chrysotile (12001295) or aluminum-silicate (12141467) ceramic fibers (RCFs) after which they were sham exposed or exposed to sidestream cigarette smoke 5 days per week for 4 weeks. After exposure the rats were killed and their lungs removed. Some lungs were examined for histological changes. The RNA was extracted from other lungs and analyzed for mRNA coding for matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), tissue inhibitors of MMP-1 (TIMP-1) and MMP-2 (TIMP-2), and type-I and type-IV collagen by a reverse transcription/polymerase chain reaction assay. All treatments significantly increased MMP-1 mRNA expression. The increase induced by chrysotile plus cigarette smoke was additive. Neither chrysotile, the RCFs, nor cigarette smoke alone affected MMP-2 mRNA expression. Combined exposure to chrysotile plus cigarette smoke or RCFs plus cigarette smoke significantly increased the level of MMP-2 mRNA expression. TIMP-1 mRNA expression was not detected in control, chrysotile or RCF exposed lungs. Cigarette smoke alone and cigarette smoke plus chrysotile induced TIMP-1 MRNA expression. TIMP-2 mRNA expression was not induced by either RCFs or chrysotile. Cigarette smoke significantly decreased TIMP-2 mRNA expression. This effect was not altered by RCF nor chrysotile coexposure. Neither RCFs nor chrysotile increased type-I collagen mRNA expression. Cigarette smoking decreased type-I collagen mRNA expression. Expression of type-IV collagen mRNA was not detected in any of the lung tissue samples. Foreign body giant cells and mononuclear cell infiltration around bronchioles were observed in lung tissues from chrysotile and chrysotile plus cigarette smoke exposed rats. No treatment related histopathological changes were seen in lung tissues from the other groups. The authors conclude that MMPs and TIMPs may be associated with remodeling of lung tissues induced by exposure to mineral fibers and cigarette smoke.

Journal Article

Abstract  The use of fibre-shaped nanomaterials in commercial applications has met with concern that they could cause health effects similar to those seen with pathogenic fibres such as certain forms of asbestos. Of the attributes which form the fibre pathogenicity paradigm, fibre length is thought to be a critical factor in determining fibre toxicity. We have previously shown that carbon nanotubes display such length-dependent pathogenicity but it remains unclear if other forms of fibrous nanomaterials conform to the fibre pathogenicity paradigm. As such, our aim is to determine the generality of this hypothesis by asking whether a radically different form of fibrous nanomaterial, nickel nanowires, show length-dependent pathogenicity. Our results indicate that nickel nanowires synthesised to be predominantly long (>20 μm) show the ability to elicit strong inflammation in the mouse peritoneal model in a dose-dependent manner; inflammation or fibrosis was not seen with the short (<5 μm) nanowires. This length-dependent response was also seen after lung aspiration and within a macrophage in vitro model adding further weight to the contention that fibre length is an important driver of hazard potential. This may have important implications when considering the hazard posed by fibrous nanomaterials and their regulation in workplaces.

DOI
Journal Article

Abstract  Combined with the foam stability of air-entraining admixtures (AEAs), the effect of salt admixtures (including CaCl2, Ca(NO3)(2), Na2SO4 and NaNO2) on morphology of air-voids in cement paste with a couple kinds of air-entraining admixtures (including SJ-2 and DH-9) was examined by means of SEM. In accordance with foam stability and the morphology, air content of fresh concrete was studied and analyzed more deeply. The results pointed out that these salts mitigated the foam stability of SJ-2 solution, and the deteriorated effect of CaCl2 and Ca(NO3)(2) was more obvious. By contrast, these salts seemed to make no difference to the foam stability, but CaCl2 and Ca(NO3)(2) reduced the foaming power of DH-9 solution. The walls of air voids in cement paste without using AEAs were compact. Differently, it was a distinct shell that formed around most of the entrained air voids with AEAs. This shell connected with capillary pores. For SJ-2 mixed, the air content of fresh air-entrained concretes was decreased by CaCl2 and Ca(NO3)(2), but was enhanced by Na2SO4 and NaNO2; for DH-9 mixed, with the increasing usage of CaCl2, Ca(NO3)(2), Na2SO4 or NaNO2, the air content was rising gradually.

Journal Article

Abstract  Associations between inorganic fiber burdens and job category in the lungs of industrial workers were examined. Lung tissue sections were collected from 21 workers employed in gold, zinc, and copper mining, 18 iron foundry workers, 22 noniron foundry workers, four welders, three sandblasting workers, four construction workers, three technical or professional workers, seven workers in 'miscellaneous trades', 13 former asbestos (1332214) workers with mild asbestosis, and 20 persons from the general population (controls). The tissue samples were digested in aqueous sodium-hypochlorite. After drying, the digests were prepared for analysis for quartz (14808607) and other elements by transmission electron microscopy and energy dispersive spectroscopy. The quartz analyses were also performed by X-ray diffraction analysis. The highest quartz concentrations varied from 0.69 to 3.90 million particles per milligram dry lung tissue (mp/mg) and were found in tissues from the miners, iron foundry, and sandblasting workers. Lung quartz burdens in the workers in the other occupations varied from 0.05 to 0.65mp/mg, the highest concentrations in these groups being found in the welders and technical and professional personnel. The quartz concentrations in the asbestos workers and controls averaged 0.40 and 0.23mp/mg, respectively. High levels of metallic particles were found in the lungs of welders and iron foundry workers, averaging 6.13 and 1.10mp/mg, respectively. The particles consisted primarily of aluminum (7429905), nickel (7440020), manganese (7439965), cadmium (7440439), and chromium (7440473). When stratified according to fiber characteristics, the highest concentrations of long fibers were found in noniron foundry workers and asbestos workers. High concentrations of ferruginous bodies were also found in these groups. The noniron foundry workers had been exposed to ceramic and asbestos fibers. The authors conclude that the composition of the particles found in the lungs of these workers can be explained on the basis of their work histories. The broad range of particle types identified demonstrate the complexity of trying to determine disease origins in these occupational settings.

Journal Article

Abstract  The potential of microscopic characterization of fibrous and environmental particles was discussed with two examples from recent laboratory experience. Examples of the characterization of surface modified asbestos (1332214) particles using conventional secondary ion mass spectroscopy, electron spectroscopic imaging, and electron energy loss spectroscopy were given. The secondary ion images of titanium and titanium-oxide may be used to selectively indicate the contour of the asbestos fiber. The titanium ion images demonstrated that, within the lateral resolution of the ion microprobe, the titanium reacted fairly evenly over the selected area of the chrysotile (12001295) surface and no evidence of any significant build up of localized titanium containing compounds was found. The application of the scanning proton microprobe (SPM) method to characterize the North Sea aerosol was discussed. An attempt was made to quantitatively estimate from field measurements the atmospheric input of heavy metals into the North Sea and to evaluate the nature of the aerosol particles responsible for this flux. By using the scanning proton beam it was possible to reveal elemental distributions within a single aerosol particle structure. Detected total amounts for sulfur (7704349), chlorine (7782505), potassium (7440097), calcium (7440702), titanium (7440326), vanadium (7440622), chromium (7440473), iron (7439896), nickel (7440020), and zinc (7440666) were in the range of 0.01 picograms for zinc to 390 picograms for chlorine.

Journal Article

Abstract  A study of the prevalence of obstructive lung disease in the general population was conducted. The cohort consisted of 3370 persons living in and around Bergen, Norway. They completed a questionnaire to obtain information on biodemographic characteristics, job history, and any occupational exposures to asbestos (1332214), quartz (14808607), wood dust, chromium (7440473), nickel (7440020), platinum (7440064) fumes, fumes in the aluminum industry, and smoking. A total of 1275 subjects were given a medical examination that included spirometric testing. Of these, 38 had asthma, 65 had chronic obstructive pulmonary disease (COPD), and 52 had forced vital capacity volume and 1 second forced expiratory volume (FEV1) values indicative of airflow limitation (airflow limitation group). In the subjects with asthma, COPD, and airflow limitation, the average decrements in FEV1 were 10, 37, and 40%, respectively. The FEV1 decrements increased with age in subjects with COPD and airflow limitation, but not in those with asthma. The prevalence rates for asthma, COPD, and airflow limitation were estimated to be 2.4, 5.4, and 4.5%, respectively. The prevalence of asthma was not affected by smoking status. The prevalence of COPD and airflow limitation was significantly higher in smokers and persons who lived in urbanized areas. Age and smoking were significant risk factors for COPD and airflow limitation after adjusting for sex. Having a job that involved exposure to one or more of the agents was a significant risk factor for asthma and COPD. COPD was significantly associated with exposure to quartz, dust, chromium, nickel, and platinum fume, and aluminum production, processing, and welding. None of the exposures was significantly associated with airflow limitation. When the analysis was restricted to persons older than 50 years, asbestos and quartz exposures were significantly associated with airflow limitation after adjusting for sex, age, and smoking. The authors conclude that COPD is a common disorder in northwestern European populations. Occupational exposure to certain airborne agents and smoking are significant risk factors.

Journal Article

Abstract  Energy-dependent gamma ray shielding properties were measured as a function of gamma ray energy for a low permeability asphalt concrete that is used as a cap to prevent water infiltration into radioactive waste sites, Experimental data were compared to ISO-PC point kernel shielding calculations, Calculated dose equivalent rates compared well with experimental values, especially considering the poor detector resolution involved, The shielding properties of the asphalt concrete closely resembled those of aluminum, The results presented can be used to determine the asphalt concrete thickness required to reduce dose equivalent rates from several gamma ray emitting radionuclides.

Journal Article

Abstract  There is evidence to support the role of a number of environmental factors in Alzheimer disease (AD). This study examines the role of chemical and physical exposures in the occupational environment. The sample included 170 patients with AD and 170 medical-practice-based controls, matched for age and sex, who were assessed for histories of occupational exposures to a range of chemical and physical agents, including hydrocarbon solvents, lead, mercury, organophosphates, aluminum, asbestos and other silicates, vibration, and physical underactivity. Occupational histories were obtained from informants for both patients and controls. Exposure was assessed by a panel of occupational hygienists, blinded to the case or control status of each subject, using the occupational histories and the Job-Exposure Matrix of the U.S. National Institute for Occupational Safety and Health. No statistically significant associations were found between any of the exposures and the occurrence of AD, either in the overall study group or in patients with a family history of AD. The findings suggest the absence of any occupational cause for AD.

Journal Article

Abstract  Much concern has been raised over the health consequences of workers exposed to carbon nanotubes. In order to characterize multi-wall carbon nanotubes (MWCNT) suspended in a phosphate-buffered saline containing 0.1% Tween 80 for an intratracheal instillation study. Length and width distributions of the MWCNT fibers, dispersion of MWCNT in the suspension and in the lung tissue and the MWCNT contents of metal impurities were investigated. Arithmetic mean length and width of the MWCNT fibers as measured on scanning electron microscope (SEM) photographs were 5.0 microm and 88 nm, respectively, and fibers longer than 5.0 microm were 38.9% of all fibers measured. Dynamic light scattering size measurement revealed that 5-min ultrasonication, together with addition of Tween 80 into the suspension, decreased the hydrodynamic diameters of the agglomerated MWCNT to those of finer particles below 1.0 microm. SEM observation showed good dispersion of MWCNT in the suspension, and in the alveoli on Day 1 after instillation. Concentration of iron, chromium and nickel in the MWCNT were 4,400, 48 and 17 ppm (wt/wt), respectively, all of which were below levels that would elicit positive pulmonary toxic responses to these metals. The results suggest that well-dispersed, long and thin MWCNT fibers exhibit asbestos-like pathogenicity in the lung.

DOI
Journal Article

Abstract  A sewage system, 300 km long, showed superficial deterioration of concrete just 2 years after construction. In order to re-habilitate the structure, it was necessary to identify the main mechanism of deterioration and to understand the heterogeneous distribution of the damage observed. The study was performed in a three stepped program: site investigation and sampling, laboratory tests and concrete petrography. During the site inspection it was recognized that there was dissolution of the concrete in some sectors of the structure, with the aggregate particles protruding in relation to the undulated surface. In some places a white to yellowish putty-like product could be excavated by hand. The main deterioration was observed above the water level. The composition of the atmosphere inside the sewer was assessed and a high content of hydrogen sulfide was detected. Sampling was performed in different structural elements which showed diverse exposition to the aggressive environment. Impregnated thin sections of concrete with fluorescent yellow dye were analyzed by optical microscope. Concrete petrography showed to be crucial for the diagnoses. The study showed that the putty-like product was composed by gypsum with small residual particles of siliceous sand which resisted to the acid attack. SEM/EDS was used to evaluate the content of sulfur in different sections of the concrete cores and also to characterize the putty-like product at the surface of the concrete. This study led to the confirmation of the presence of an extensive sulfuric acid attack with rather minor sulfate attack within the concrete due to the exposition to aggressive environment. It also showed that behind the superficial deteriorated level, the concrete was sound with no signs of internal deleterious reactions. Ammonium content in residual water might have also contributed to the superficial deterioration of the concrete sewer.

DOI
Journal Article

Abstract  A new rapid method for the determination of Ra-226 in environmental samples has been developed at the Savannah River Site Environmental Lab (Aiken, SC, USA) that can be used for emergency response or routine sample analyses. The need for rapid analyses in the event of a Radiological Dispersive Device or Improvised Nuclear Device event is well-known. In addition, the recent accident at Fukushima Nuclear Power Plant in March, 2011 reinforces the need to have rapid analyses for radionuclides in environmental samples in the event of a nuclear accident. Ra-226 (T1/2 = 1,620 years) is one of the most toxic of the long-lived alpha-emitters present in the environment due to its long life and its tendency to concentrate in bones, which increases the internal radiation dose of individuals. The new method to determine Ra-226 in environmental samples utilizes a rapid sodium hydroxide fusion method for solid samples, calcium carbonate precipitation to preconcentrate Ra, and rapid column separation steps to remove interferences. The column separation process uses cation exchange resin to remove large amounts of calcium, Sr Resin to remove barium and Ln Resin as a final purification step to remove Ac-225 and potential interferences. The purified Ra-226 sample test sources are prepared using barium sulfate microprecipitation in the presence of isopropanol for counting by alpha spectrometry. The method showed good chemical recoveries and effective removal of interferences. The determination of Ra-226 in environmental samples can be performed in less than 16 h for vegetation, concrete, brick, soil, and air filter samples with excellent quality for emergency or routine analyses. The sample preparation work takes less than 6 h. Ra-225 (T1/2 = 14.9 day) tracer is used and the Ra-225 progeny At-217 is used to determine chemical yield via alpha spectrometry. The rapid fusion technique is a rugged sample digestion method that ensures that any refractory radium particles are effectively digested. The preconcentration and column separation steps can also be applied to aqueous samples with good results.

Journal Article

Abstract  BIOSIS COPYRIGHT: BIOL ABS. Induction of chrysotile produced in Mang ai to the production of nitrogen oxide (NO) and effects of mixed rare earths (MRE), sodium selenite (SS) and aluminium citrate on the production of NO in alveolar macrophage (AM) induced by asbestos fiber were observed by in vitro cell culture technique and determination of nitrite ion content in the culture medium. Results showed that chrysotile fiber could increase nitrite ion content in the culture medium, with an obvious dose-dependent relationship. MRE, selenite, and aluminium citrate all could inhibit the production of NO in AM induced by asbestos, and its inhibitory effects increased with the concentration of the above-mentioned chemicals. It suggests antagonism of MRE and selenite to pathogenicity of asbestos may be used in practice.

DOI
Journal Article

Abstract  This work deals with investigations on effect of chemically and thermally resistant carbon fibre (CF) additives of various mechanical treatment on structure formation and properties of autoclaved aerated concrete (AAC). It was established that various methods of CF crushing, such as mixing with sand pulp, chopping, grounding, milling in dry way, milling in wet way cause different fineness of disintegrated CF particles and that along with increase in fineness, the crystallinity of AAC binding material is growing what leads to the following: increase in compressive strength by 6-22%; after exposure at temperature of 700 C, decrease in thermal deformation by 5-20%; decrease in mass loss by 7-20%. Upon addition of mechanically not treated CF of 0.1%, the flexural strength increases by 29% versus that of AAC without CF additive. The effect of added mechanically treated CF on flexural strength is less than that of not treated CF. Due to increased CF fineness, the flexural strength increment drops from 21% to 4%. Basing on the results obtained, one can draw a conclusion that CF particles resulted in mechanical treatment have an activated surface and can serve as nuclei of crystallization during the hardening of AAC binding material, which contains a mechanically treated CF additive, thus causing increase in crystallinity of hardened binding material and, consequently, improved performance of AAC. (C) 2011 Elsevier Ltd. All rights reserved.

Journal Article

Abstract  In vitro model systems have recently been developed to investigate the toxicity of chemical, microbial and physical agents in normal human tissues and cells from many of the major tissue sites of high cancer incidence. Pathobiological endpoints used in these studies include alterations in incorporation rates of precursors into DNA, RNA and protein, in the clonal growth rate of cultured cells and in DNA structure (e.g. single-strand breaks, DNA-protein crosslinks and chemical-DNA adducts) and the induction of differentiation, chromosomal and karyotypic abnormalities, mutations and neoplastic transformation. These systems have been used to study a variety of complex mixtures and individual substances, including cigarette smoke components such as benzo[a]pyrene and N-nitrosamines, formaldehyde, fecapentaenes, asbestos, and nickel and chromium ions. In addition, increasing awareness of the role of oncogenes in human carcinogenesis has led to studies involving transfection experiments with oncogenes and hepatitis B viral genes in normal human cells.

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Journal Article

Abstract  The Shi-Hang zone is an important NE trending Mesozoic magmatic belt composed of granites with relative high epsilon(Nd)(t) values and young T-DM model ages in South China. However, the petrogenesis and the tectonic environment for the Shi-Hang zone magmatic rocks remain controversial. We report here mineral chemistry, geochemical and Sr-Nd-Hf isotopic data for the Cailing and Furong granites and mafic microgranular enclaves (MMEs) from the Qitianling granite batholith in southern Hunan province, South China. The Qitianling granite batholith is a multi-staged composite pluton with three phases (Cailing, Furong, and Huangtangling) according to their ages and petrography. The Cailing (163-160 Ma) and Furong (157-153 Ma) phases are mainly composed of porphyritic amphibole-biotite monzogranite, and they share similar geochemical and isotopic characteristics. Both of them show similar SiO2 contents from 66.50 to 70.28%, and metaluminous A/CNK values of 0.80 to 0.98. The granites are characterized by high contents of large ion lithosphile elements (LILE) such as Rb, Th, U, Pb; high field strength elements (HFSE) such as Nb, Ta, Zr, Hf; and Zr + Nb +Ce + Y contents >350 ppm, and high 10,000*Ga/Al ratios >2.6. Chondrite-normalized REE patterns show relative enrichment of light rare earth elements (LREEs) and significant negative Eu anomalies. Mineralogical and geochemical features suggest that the Cailing and Furong granites are A-type, which can be further classified as A(2) subtype. They have relatively lower (Sr-87/Sr-86); ratios (0.7091-0.7132), higher epsilon(Nd)(t) values (-5.5 to -7.6) and younger Nd isotopic model ages (1.48-1.56 Ga) than those common S-type granites in South China. Zircon epsilon(Hf)(t) values vary from -8.1 to -3.7. The MMEs in the Cailing phase show similar trace element and Sr-Nd isotopic characteristics with the host granites. But zircons from the MMEs show different epsilon(Hf)(t) values (-6.4-+2.6) with those from the host granites (-8.1 to -3.7). This indicates that the MMEs and host granites were crystallized from different sources of magmas, providing direct evidence for mafic-felsic magma mixing processes. The isotope data indicate that the Cailing and Furong granites from the Qitianling batholith were derived from a hybrid magma consisting of about 80% felsic magma derived from old crust and about 20% mantle-derived mafic magma. The strong magma mixing at about 160155 Ma caused by intra-arc rifting or back arc extension related to subduction of the Paleo-Pacific plate, is favored to explain the petrogenesis of the Cailing and Furong granites, as well as the Shi-Hang zone. (C) 2011 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

WoS
Journal Article

Abstract  During the recent decades, rapid urbanization growth has led to even faster growth of motor vehicles and especially in large cities. Hence, evaluation of the actual level of traffic emissions has gained more interest. This paper, for the first time, presents a bottom-up approach for evaluation of vehicular emissions in Tehran- the capital of Iran- using the International Vehicle Emission (WE) model. The IVE model uses local vehicle technology levels and its distributions, power based driving factors, vehicle soak distributions and meteorological parameters to tailor the model for specific evaluation of emissions. The results of this study demonstrate that carbon monoxide (CO) emission with 244.45 ton/hr during peak traffic hour is the most abundant criteria pollutant. About 25% of this quantity is emitted during start-up periods. Other pollutants such as NOx, VOCs, PM, VOCevap and SOx are ranked after CO accordingly. Also, carbon dioxide (CO2) emissions of 1744.22 ton/hr during the study period indicate that light vehicles are responsible for more than 82% of this amount. Based on IVE's evaluation, about 25% of the total vehicle emissions in Tehran come from districts 2, 4 and 6 respectively. It has further been inferred that the development of public transportation systems and proper land-use and urban spatial planning for various centers in these districts are essential.

Journal Article

Abstract  Asbestos has been implicated in the pathogenesis of interstitial lung diseases including asbestosis. Tissue factor (TF) initiates blood coagulation in vivo contributing to inflammation and tissue remodeling via extravascular fibrin deposition and signaling for profibrogenic mediators. We hypothesized that asbestos could induce TF expression by lung epithelial cells. We found that TF mRNA and TF-dependent procoagulant activity were induced in asbestos-treated Beas-2B human airway epithelial cells, which we used as a model system. The effect was increased by crocidolite and chrysotile versus control particulates, including titanium dioxide (TiO2) and Wollastonite (W). Transcription factors that bind the TF gene promoter, including NF-kappaB, AP1 and Sp1, were induced by asbestos while TF mRNA was unstable. TF mRNA was inhibited by mithramycin in asbestos-treated as well as control cells suggesting that Sp1 contributes to TF maintenance in Beas-2B cells. Sp1 knockdown with specific siRNA decreased TF antigen, which is consistent with Sp1-mediated control of TF in Beas-2B cells. The results demonstrate that asbestos induces TF expression in lung epithelial cells in vitro, representing a newly recognized potential mechanism by which asbestos may modulate epithelial cell responses germane to lung remodeling. The mechanism involves alterations in steady-state TF mRNA that do not involve posttranscriptional regulation, implicating control of TF gene expression at the transcriptional level through Sp1 or other transcription factors.

Journal Article

Abstract  The mechanisms underlying asbestos-induced pulmonary toxicity are not fully understood. Alveolar epithelial cell (AEC) apoptosis by iron-derived reactive oxygen species (ROS) is one important mechanism implicated. The two major pathways regulating apoptosis include (i) the mitochondrial death (intrinsic) pathway caused by DNA damage, and (ii) the plasma-membrane death receptor (extrinsic) pathway. However, it is unknown whether asbestos activates either death pathway in AEC. We determined whether asbestos triggers AEC mitochondrial dysfunction by exposing cells (A549 and rat alveolar type II) to amosite asbestos and assessing mitochondrial membrane potential changes (deltapsi(m)) using a fluorometric technique involving tetremethylrhodamine ethyl ester (TMRE) and mitotracker green. Unlike inert particulates (titanium dioxide and glass beads), amosite asbestos caused dose- and time-dependent reductions in deltapsi(m). Asbestos-induced deltapsi(m) was associated with the release of cytochrome c from the mitochondria to the cytoplasm as well as activation of caspase 9, a mitochondrial-activated caspase. In contrast, a lower level of caspase 8, the death receptor-activated caspase, was detected in asbestos-exposed AEC. An iron chelator (phytic acid or deferoxamine) or a hydroxyl radical scavenger (sodium benzoate) each blocked asbestos-induced reductions in deltapsi(m) and caspase 9 activation, suggesting a role for iron-derived ROS. Finally, Bcl-X(L), a mitochondrial antiapoptotic protein that prevents cell death by preserving the outer mitochondrial membrane integrity, blocked asbestos-induced decreases in A549 cell deltapsi(m) and reduced apoptosis as assessed by DNA fragmentation. We conclude that asbestos-induced AEC apoptosis results from mitochondrial dysfunction, in part due to iron-derived ROS, which is followed by the release of cytochrome c and caspase 9 activation. Our findings suggest an important role for the mitochondria-regulated death pathway in the pathogenesis of asbestos-associated pulmonary toxicity.

Journal Article

Abstract  The asbestiform mineral balangeroite [(Mg,Fe2+,Fe3+,Mn2+)42Si16O54(OH)36], whose toxic potential is unknown, is associated with chrysotile asbestos in the western Alps (Balangero mine, Piedmont, Italy). In order to examine whether such fibers may contribute to the oxidative damage produced by local asbestos dusts when inhaled, balangeroite was studied by means of both cell-free and cellular tests, comparing the results with those concerning the most pathogenic asbestos form, crocidolite. Similarly to the crocidolite surface, iron was mobilized from balangeroite by chelators, to a different extent: deferoxamine > ascorbic acid > ferrozine. Poorly coordinated surface ions, as evaluated from the adsorption of NO as a probe molecule (by both calorimetry and infrared spectroscopy), are even more abundant on balangeroite than on crocidolite. The spin trapping technique shows that surface iron-derived Fenton activity (HO* from H2O2) is similar for the two fiber types, while a pretreatment in ascorbic acid, by reducing previously oxidized surface iron, activates the potential to cleave a C-H bond (yielding *CO2- from formate anion). Balangeroite, like crocidolite, produces nitrite accumulation, lipid peroxidation, and NO synthase activation in a human lung epithelial cell line (A549). All these findings, regarded as features related to the toxic potential of asbestos, suggest that balangeroite may be a potentially hazardous fiber per se and could be partly responsible for lung diseases reported in epidemiological studies in exposed miners.

Journal Article

Abstract  Soot FR 101, Printex 90 and Chrysotile B are frequently found in indoor air pollutants phagocytized by alveolar macrophages (AM) involved in inflammatory pulmonary processes as, e.g. in cytokine secretions. The transcription factor NF-kappaB has a role in the trans-duction pathway of proinflammatory cytokines like IL-1beta, IL-6 and TNF-alpha. We therefore investigated whether the transcription factor NF-kappaB and subsequent inflammatory cytokine secretions by AM are induced by exposure to these particles compared to the inert TiO2. AM were incubated for 90 min at particle concentrations of up to 100 microg/10(6) cells. Sequential reverse transcription and semiquantitative cDNA amplification (RT-PCR) was used to measure NF-kappaB and cytokine mRNA expressions. Compared to control exposures these particles induced an up to 4.6-fold increase in gene expression of the transcription factor NF-kappaB (p < 0.01), resulting in up to 12.9-fold enhanced transcription rates of IL-1beta, IL-6 and TNF-alpha (p <0.05). The particles and fibre dependent increases in mRNA reached maximum levels at 90 min post exposure. After an exposure time of 8 hrs, IL-1beta, IL-6 and TNF-alpha proteins, measured by enzyme-linked immunosorbent assays (ELISA), were significant elevated in supernatants of AM, revealing an up to 30.5-fold increase in TNF-alpha secretion rates (p <0.01). Our results suggest that exposure of human AM to soot FR 101, Printex 90, TiO2 and Chrysotile B induce the transcription and production of proinflammatory cytokines via NF-kappaB and may play an important role in the pathogenesis of airway disease and lung parenchymal injury.

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