SEARCH · PubMed Health

Results for “ASBESTOS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources

PubMed2006

[Prophylactic examinations of workers formerly employed in asbestos processing plants: outcome of the Amiantus project in 2000-2004].

BACKGROUND: Prophylactic examinations of workers formerly employed in asbestos processing plants were performed by virtue of the Act, dated 19 June 1997, putting a ban on the production of asbestos-containing products. To enforce the provisions of the Act, the Ministry of Health has initiated the Amiantus project implemented by 13 Occupational Medicine Centers throughout the country and coordinated by the Nofer Institute of Occupational Medicine (IMP) in Lódź. MATERIAL AND METHODS: All the Centers perform diagnostic procedures according to the same criteria (clinical, radiological, spirometric and histological), based on the 1997 Helsinki criteria, to diagnose asbestos-related diseases. A specific "Examination Form", developed for the needs of the Amiantus project, is completed by an occupational physician during examinations and sent to the IMP, where health effects in the whole population covered by the project are monitored. Periodical medical examinations are performed at least every three years and they include: general examination, chest x-ray, resting spirometric examination and supplementary examinations (e.g., resting gasometric examination) or other diagnostic examinations if necessary (e.g., computed tomography). RESULTS: Owing to the project implementation, it was possible to collect in the database information on 5466 persons who underwent 8763 prophylactic examinations in 2000-2004. Of the total population examined during a five-year period, occupational disease was certified in 728 (13%) persons. Asbestosis was diagnosed in 790 persons, lung cancer in 19 persons and pleural mesothelioma in 12 persons. Pleural changes in x-ray imaging were found in 1662 (30%) persons and opacities in pulmonary parenchyma in 2088 (38%) persons. Having compared these results with those from previous examinations, the total health condition deterioration was observed in 882 (16%) persons, including worsening of the lung x-ray imaging in 512 (9%) persons. An analysis showed the highest incidence of asbestos-related pathologies in workers of asbestos-cement plants. The collected data also confirmed an upward trend in the incidence of asbestosis and changes in the lung x-ray imaging related to age, duration of employment and latency. CONCLUSION: The implementation of the Amiantus project has contributed to an increased detection of pathologies related with exposure to asbestos fibers. A growing proportion of radiograms, which indicate worsening of health condition provides evidence that morbid processes in the respiratory system are progressing in persons who in the past were occupationally exposed to asbestos dust.

Adult↗

PubMed1995

[Longitudinal study of radiologic anomalies in subjects working in asbestos-insulated buildings].

The respiratory effects of environmental pollution by asbestos was examined in a cohort of subjects working inside university buildings partly insulated with asbestos containing materials (University of Jussieu in Paris). The present study concerned 727 subjects having undergone two standard radiographic examinations (postero-anterior and oblique chest x-ray) in the period 1981-1992. The first examination was realized between 01/01/81 and 31/12/85 and the second examination took place between 01/01/86 and 31/12/92. The subjects were classified into three groups according to their exposure status: the group G1 consisted of 161 workers occupationally exposed to asbestos; the group G2 comprised 416 subjects working for at least 15 yr in asbestos-insulated buildings without known occupational exposure to asbestos; the group G3 consisted of 150 workers working for at least 15 yr in the university with no known exposure to asbestos. Whatever the radiological abnormalities considered, no significant difference was observed between G2 and G3 in cross-sectional analyses of the two phases. The group G1 exhibited a significantly higher prevalence of pleural thickening compared to the other exposure groups after adjustment for confounding variables. Detailed examination of oblique x-ray allowed to confirm that pleural thickening were largely due to extrapleural fat. Concerning the changes in pleural abnormalities between the two phases of the study, no difference was observed between G2 and G3. This study was unable to show any excess of radiographic chest abnormalities among subjects working in asbestos-insulated buildings compared to non-exposed subjects. However, the participation in the second phase of examination was 51.2%. The study is still on-going. Therefore, it would be necessary to continue to follow-up the subjects because respiratory disorders could occur after a long latent period.

Adult↗

PubMed1998

[Clinical evaluation of benign asbestos pleurisy].

Seventeen cases of benign asbestos pleurisy were evaluated clinically. All cases were male and almost all cases were more than 60 years-old. Most cases presented with chief complaints of chest pain and dyspnea, but 2 cases had no complaints. Pleural effusion appeared predominantly in the right side. Six cases had 2 or 3 episodes of pleural effusion, and 1 case had 5. Ten cases had an occupational history of asbestos exposure in shipyards and 5 other cases had a history in building construction. Almost all cases had more than 30 years of exposure to asbestos and benign asbestos pleurisy appeared after more than 30 years from the first exposure to asbestos. Among the patients, 6 cases had diffuse pleural thickening and 2 cases had malignancies. Pleural fluid was bloody in 14 of 17 cases (82%) and all pleural fluid showed an exudate. Lymphocytes represented 70% and eosinophils 15% of the cellular population of the pleural fluid. Hyaluronic acid in pleural fluid in cases of benign asbestos pleurisy averaged 29.5 micrograms/ml, which was significantly (p < 0.05) lower than in malignant pleural mesothelioma. Leukocytosis in peripheral blood and a high CRP value were uncommon in benign asbestos pleurisy.

Aged↗

PubMed1998

[Asbestos: current knowledge and perspectives].

Diseases due to asbestos inhalation are not only a concern for occupational physicians, but also for general practicioners and pneumologists. The real or supposed risk has extended beyond the factories employing "primary asbestos workers" to thousands of people exposed to this material or simply working in buildings insulated with asbestos. The spectrum of asbestos-related diseases has changed: asbestosis (parenchymal fibrosis due to asbestos) tends to disappear, whereas the incidence of pleural lesions, which can be associated with lower cumulative exposures, increases. Patients with asbestos related diseases do not die any more from respiratory failure but from late neoplastic complications, such as mesothelioma and lung cancer. The lack of interest and of training in occupational medicine leads to an underrecognition and an underestimation of cancers due to asbestos by the physicians. Recent progresses in CT imaging and evaluations of exposure to fibers through mineralogical analysis of lung samples have led to improve the diagnostic approach of fiber-related diseases.

Asbestosis↗

PubMed1986

In vitro cytotoxicity of chrysotile asbestos to human pulmonary alveolar macrophages is decreased by organosilane coating and surfactant.

Human pulmonary alveolar macrophages were used to quantitate the cytotoxic effect of surface-altered chrysotile asbestos. Little difference was observed in mortality between chrysotile asbestos that was surface-treated to a 42% extent by a hydrophobic organosilane or untreated chrysotile. Little or no effect on mortality was observed when human pulmonary alveolar macrophages were cultured with untreated chrysotile or acid-leached asbestos in the presence of 10 mM dipalmitoyl lecithin. However, when human pulmonary alveolar macrophages were cultured with a hydrophobically-treated (to a 42% or 95% extent) chrysotile asbestos in the presence of 10 mM dipalmitoyl lecithin, a statistically significant decrease in mortality was observed compared to untreated chrysotile. No mutagenic activity was observed when V79 cells were cultured with acid-leached, or 42% hydrophobically-treated chrysotile asbestos, even when human pulmonary alveolar macrophages were included as an activation source. The 95% hydrophobically-treated and acid-leached chrysotile also exhibited decreased binding of benzo[a]pyrene compared to untreated chrysotile asbestos.

Adult↗

PubMed1996

Elevated interleukin-8 in the alveolitis of individuals with asbestos exposure.

Asbestosis is a fibrotic and inflammatory interstitial lung disease occurring after chronic occupational exposure to asbestos. An alveolitis has been described with activated alveolar macrophages and increased neutrophils as sampled by bronchoalveolar lavage (BAL). Animal models and in vitro studies demonstrate that asbestos can stimulate alveolar macrophages to release neutrophil chemotactic factor. We performed BAL on 18 nonsmoking individuals with asbestos exposure and observed a twofold increase in percent neutrophils recovered. Alveolar macrophages cultured in vitro from the asbestos-exposed individuals spontaneously released significant amounts of the neutrophil chemotaxin, interleukin-8 (IL-8). In addition, the alveolar macrophages expressed a 2.7-fold increase in steady state mRNA levels compared to unexposed normal controls utilizing the reverse transcriptase/polymerase chain reaction. In vitro experiments confirmed that crocidolite or chrysotile asbestos could stimulate the release of IL-8 from mononuclear phagocytes in a dose-dependent fashion. We conclude that asbestos exposure causes a mild neutrophilic alveolitis, and that IL-8 is one potential mediator capable of contributing to this inflammation in the lower respiratory tract.

Asbestos, Crocidolite↗

PubMed1978

Effects of asbestos on epithelioid cell lines.

The in vitro effects of asbestos fibers on the growth and viability of CHO cells, an epithelioid cell line derived from Chinese hamster ovary, and on K-22 cells, an epithelial cell line derived from rat liver, have been studied. Relatively low concentrations of asbestos (10 micrograms/ml) were quite cytotoxic to both cell types. A sample of chrysotile asbestos was more toxic than samples of crocidolite or amosite. The toxic factor could not be extracted from the asbestos and toxicity occurred only if there was physical contact between the fibers and the cells. Although the phorbol ester class of tumor promoters induces the synthesis of plasminogen activator in various cell cultures, asbestos did not induce this protease in epithelioid or fibroblast cell cultures. The results obtained are compared to previous in vitro results obtained with fibroblast or macrophage cultures and are discussed in terms of their possible relevance to asbestos-induced fibrosis and tumorigenesis.

Animals↗

PubMed2004

Modulation of genotoxic effects in asbestos-exposed primary human mesothelial cells by radical scavengers, metal chelators and a glutathione precursor.

The genotoxicity of asbestos fibers is generally mediated by reactive oxygen species (ROS) and by insufficient antioxidant protection. To further elucidate which radicals are involved in asbestos-mediated genotoxicity and to which extent, we have carried out experiments with the metal chelators deferoxamine (DEF) and phytic acid (PA), and with the radical scavengers superoxide dismutase (SOD), dimethylthiourea (DMTU) and the glutathione precursor Nacystelyn trade mark (NAL). We investigated the influence of these compounds on the potency of crocidolite, an amphibole asbestos fiber with a high iron content (27%), and chrysotile, a serpentine asbestos fiber with a low iron content (2%), to induce micronuclei (MN) in human mesothelial cells (HMC) after an exposure time of 24-72 h. Our results show that the number of crocidolite-induced MN is significantly reduced after pretreatment of fibers with PA and DEF. This effect was not observed with chrysotile. In contrast, simultaneous treatment of cells with asbestos and the OH*scavenging DMTU or the O2- -scavenging SOD significantly decreased the number of MN induced by chrysotile and crocidolite. In particular, DMTU almost completely suppressed micronucleus induction by both fiber types. A similar effect was observed in the presence of the H(2)O(2)-scavenging NAL after chrysotile treatment of HMC. By means of kinetochore analysis, it could be shown that the number of clastogenic events is decreased after PA and DEF pretreatment of fibers as well as after application of the above-mentioned scavengers. Our results show that chrysotile asbestos induces an increased release of H(2)O(2) in contrast to crocidolite. Also, the iron content of the fiber plays an important role in radical formation, but nevertheless, chrysotile produces oxy radicals to a similar extent as crocidolite, probably by phagocytosis-mediated oxidative bursting.

Acetylcysteine↗

PubMed1997

Silica, asbestos, man-made mineral fibers, and cancer.

Approximately three million workers in the United States are estimated to be exposed to silica, man-made mineral fibers, and asbestos. The lung is the primary target organ of concern. Each of these substances is composed predominantly of silicon and oxygen; asbestos and silica are crystalline, and asbestos and man-made mineral fibers are fibers. Man-made mineral fibers and asbestos are used as insulating agents, with the former having generally replaced the latter in recent years. Silica is used in foundries, pottery, and brick making, and is encountered by miners. A meta-analysis of 16 of the largest studies with well-documented silica exposure and low probability of confounding by other occupational exposures, indicates a relative risk (RR) of 1.3 (95 percent confidence interval [CI] = 1.2-1.4). Lung cancer risks are highest and most consistent for silicotics, who have received the highest doses (RR = 2.3, CI = 2.2-2.4, across 19 studies). The data for mineral fibers continue to support the International Association for Research on Cancer's 1988 judgment that mineral fibers are a possible human carcinogen (Group 2B). Recent epidemiologic studies provide little evidence for lung carcinogenicity for either glass wool or rock/slag wool. Ceramic fibers, a much less common exposure than glass wool and rock/slag wool, are of concern because of positive animal studies, but there are insufficient human data. Regarding asbestos, its carcinogenicity for the lung and mesothelium is well established. With regard to the controversy over chrysotile and mesothelioma, the data suggest chrysotile does cause mesothelioma, although it may be less potent than amphibole asbestos.

Animals↗

PubMedDate not supplied

Occult exposure to asbestos in steel workers revealed by bronchoalveolar lavage.

To investigate the asbestos burden in a steelplant environment, we counted asbestos bodies (ABs) in the bronchoalveolar lavage fluid (BALF) of 65 steel workers who had retired during the previous 5 y. They had worked for at least 15 y in the same area of the plant (coke oven or blast furnace) as maintenance or production workers. On the basis of occupational anamnesis, 28 had occasional past professional exposure to asbestos; the remaining 37 workers denied any contact with asbestos. A total of 54 white-collar workers who had no occupational exposure to asbestos were included in the study as controls. An increased prevalence and concentration of ABs was found in the BALF of steel workers. Electron microscopy and EDAX analysis of AB from steel workers revealed that the core fibers were mainly amphiboles. More ABs were found in the BALF of maintenance workers than in production workers. However, the BALF from steel workers who denied any contact with asbestos revealed an increased AB burden v. controls. This demonstrates that steel workers may be subject to an occult exposure to amphiboles in the steelplant environment.

Asbestos↗

PubMed1992

Iron mobilization from crocidolite asbestos greatly enhances crocidolite-dependent formation of DNA single-strand breaks in phi X174 RFI DNA.

The ability of the iron associated with asbestos to catalyze damage to phi X174 RFI DNA was determined and compared with iron mobilized from asbestos. Asbestos (1 mg/ml) suspended for 30 min in 50 mM NaCl containing 0.5 micrograms phi X174 RFI DNA, pH 7.5, did not catalyze detectable amounts of DNA single-strand breaks (SSB). However, addition of ascorbate (1 mM) resulted in 19, 26, 7 or 8% DNA with SSB for crocidolite, amosite, chrysotile or tremolite respectively. The percentage of DNA with SSB induced by each form of asbestos was directly related to its iron content. Inclusion of desferrioxamine B, which binds Fe(III) rendering it redox inactive, completely inhibited asbestos-dependent formation of DNA SSB, suggesting that iron was responsible for catalyzing the formation of DNA SSB. Mobilization of Fe(II) from crocidolite by citrate, EDTA or nitrilotriacetate (1 mM) in the absence of ascorbate resulted in 15, 33 or 63% DNA with SSB respectively. This activity was completely inhibited by compounds considered to be .OH scavengers, i.e. mannitol, 5,5-dimethyl-1-pyrroline N-oxide or salicylate (100 mM). Preincubation of crocidolite with citrate (1 mM) for 24 h resulted in mobilization of 52 microM iron and increased ascorbate-dependent induction of DNA SSB compared with crocidolite that was preincubated without citrate. Iron mobilized by citrate was entirely responsible for crocidolite-dependent formation of DNA SSB as evidenced by complete inhibition with desferrioxamine B. Therefore, the results of the present study strongly suggest that iron was responsible for asbestos-dependent generation of oxygen radicals, which resulted in the formation of DNA SSB. Mobilization of iron by chelators, followed by redox cycling, greatly enhanced crocidolite-dependent formation of DNA SSB. Thus, mobilization of iron in vivo by low mol. wt chelators may lead to the increased production of reactive oxygen species resulting in damage to biomolecules, such as DNA.

Asbestos↗

PubMed1999

Asbestos induction of extended lifespan in normal human mesothelial cells: interindividual susceptibility and SV40 T antigen.

Normal human mesothelial cells from individual donors were studied for susceptibility to asbestos-induction of apoptosis and generation of an extended lifespan population. Such populations were generated after death of the majority of cells and arose from a subset of mesothelial cultures (4/16) whereas fibroblastic cells (5/5) did not develop extended lifespan populations after asbestos exposure. All mesothelial cultures were examined for the presence of SV40 T antigen to obtain information on (i) the presence of SV40 T antigen expression in normal human mesothelial cells and (ii) the relationship between generation of an extended lifespan population and expression of SV40 T antigen. Immunostaining for SV40 T antigen was positive in 2/38 normal human mesothelial cultures. These cultures also had elevated p53 expression. However, the two isolates expressing SV40 T antigen did not exhibit enhanced proliferative potential or develop an extended lifespan population. Asbestos-generated extended lifespan populations were specifically resistant to asbestos-mediated but not to alpha-Fas-induced apoptosis. Deletion of p16Ink4a was shown in 70% of tumor samples. All mesothelioma cell lines examined showed homozygous deletion of this locus which extended to exon 1beta. Extended lifespan cultures were examined for expression of p16Ink4a to establish whether deletion was an early response to asbestos exposure. During their rapid growth phase, extended lifespan cultures showed decreased expression of p16Ink4a relative to untreated cultures, but methylation was not observed, and p16Ink4a expression became elevated when cells entered culture crisis. These data extend the earlier observation that asbestos can generate extended lifespan populations, providing data on frequency and cell type specificity. In addition, this report shows that generation of such populations does not require expression of SV40 T antigen. Extended lifespan cells could represent a population expressing early changes critical for mesothelioma development. Further study of these populations could identify such changes.

Adult↗

PubMed1986

Follow up study of workers manufacturing chrysotile asbestos cement products.

A cohort study has been carried out of 2167 subjects employed between 1941 and 1983 at an asbestos cement factory in England. The production process incorporated the use of chrysotile asbestos fibre only, except for a small amount of amosite during four months in 1976. Measured airborne fibre concentrations available since 1970 from personal samplers showed mean levels below 1 fibre/ml, although higher levels had probably occurred previously in certain areas of the factory. No excess of lung cancer was observed in the mortality follow up by comparison with either national or local death rates, and analyses of subgroups of the workforce by job, exposure level, duration of employment, duration since entry, or calendar years of employment gave no real suggestion of an asbestos related excess for this cause of death. There was one death from pleural mesothelioma and one with asbestosis mentioned as an associated cause on the death certificate, but neither is thought to be linked to asbestos exposure at this factory. Other suggested asbestos related cancers, such as laryngeal and gastrointestinal, did not show raised risks. Although the durations of exposure were short in this study, the findings are consistent with two other studies of workers exposed to low concentrations of chrysotile fibre in the manufacture of asbestos cement products which reported no excess mortality.

Asbestos↗

PubMed1992

Extreme airborne asbestos concentrations in a public building.

Fibre concentrations of asbestos were measured in the air of a communal dining room in which the damaged ceiling had a sprayed on coating of insulation containing asbestos. The average concentration of crocidolite asbestos fibres was 4 f/cm3, 20 times the highest air concentration that appears to have been reported previously for a public building. It is concluded that although air concentrations of asbestos fibres in public buildings containing asbestos insulation materials are usually low, high concentrations can occur. This may have implications for the risk of exposed persons developing diseases associated with asbestos.

Air Pollution, Indoor↗

PubMed1996

Asbestos induces apoptosis in human alveolar macrophages.

Asbestos refers to a group of fibrous minerals implicated in the development of several lung diseases, including fibrosis (asbestosis), cancer, and malignant mesothelioma. Although major health risks exist in occupationally exposed individuals, low-level exposures of asbestos may still contribute to health problems. The mechanism by which asbestos causes lung disease is not clearly understood but has been proposed to involve the alveolar macrophage (AM). We propose that asbestos induces apoptosis of AM, resulting in the development of an inflammatory state. In this study, we examined two forms of asbestos, chrysotile (CHR) and crocidolite (CRO), along with a control fiber, wollastonite (WOL), to characterize their relative cytotoxicity and ability to stimulate apoptosis in vitro. AM were cultured for 24 h with these particulates and examined for cell viability (trypan blue exclusion) and apoptosis (morphology, levels of cytosolic oligonucleosomal DNA fragments, and DNA ladder). In the absence of a decrease in cell viability, both CHR and CRO produced changes in cell morphology consistent with apoptosis. In addition, levels of cytoplasmic oligonucleosomal DNA (Cell Death Detection enzyme-linked immunosorbent assay) were significantly enhanced for CHR (3-25 micrograms/ml) and CRO (25-75 micrograms/ml) in a dose-dependent manner (a process that was inhibitable by 10 microM Z-Val-Ala-Asp fluoromethyl ketone, an interleukin-converting enzyme inhibitor). In contrast, WOL (up to 400 micrograms/ml) produced no significant DNA fragmentation in a 24-h culture. Neither CHR nor CRO caused DNA ladder formation in 24-h cell cultures. However, in 48-h cell cultures, both CHR- and CRO-exposed cells, but not WOL, resulted in the formation of DNA ladders characteristic of apoptosis. In summary, these results suggest that, unlike nonfibrogenic particulates, low doses of asbestos fibers cause apoptosis in cultured human AM that may be an early step in the development of lung fibrosis.

Apoptosis↗

PubMed2000

Vitronectin adsorption to chrysotile asbestos increases fiber phagocytosis and toxicity for mesothelial cells.

Biological modification of asbestos fibers can alter their interaction with target cells. We have shown that vitronectin (VN), a major adhesive protein in serum, adsorbs to crocidolite asbestos and increases fiber phagocytosis by mesothelial cells via integrins. Because chrysotile asbestos differs significantly from crocidolite in charge and shape, we asked whether VN would also adsorb to chrysotile asbestos and increase its toxicity for mesothelial cells. We found that VN, either from purified solutions or from serum, adsorbed to chrysotile but at a lower amount per surface area than to crocidolite. Nevertheless, VN coating increased the phagocytosis of chrysotile as well as of crocidolite asbestos. VN coating of both chrysotile and crocidolite, but not of glass beads, increased intracellular oxidation and apoptosis of mesothelial cells. The additional apoptosis could be blocked by integrin-ligand blockade with arginine-glycine-aspartic acid peptides, confirming a role for integrins in the fiber-induced toxicity. We conclude that VN increases the phagocytosis of chrysotile as well as of crocidolite asbestos and that phagocytosis is important in fiber-induced toxicity for mesothelial cells.

Adsorption↗

PubMed1985

Production of arachidonic acid metabolites by macrophages exposed in vitro to asbestos, carbonyl iron particles, or calcium ionophore.

Consequent to asbestos deposition, alveolar macrophages (AM) accumulate at alveolar duct bifurcations where they phagocytize fibers. Because phagocytosis can stimulate the release of arachidonic acid (AA) metabolites, the possibility that secretion of these powerful mediators of inflammation might be induced by chrysotile asbestos was investigated in vitro. Rat AM were treated in vitro with chrysotile asbestos, and the cyclooxygenase products--prostaglandins, thromboxane B2 (TXB2), 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT)--and lipoxygenase products--leukotrienes (LT), hydroxyeicosatetraenoic acids (HETE)--secreted in the medium were isolated by high-performance liquid chromatography. Composition of the AA metabolites released was compared with that from those stimulated by the calcium ionophore A 23187 (20 microM) and by another particulate phagocytic stimulus, i.e., carbonyl iron beads. Calcium ionophore stimulation induced a marked release of various AA metabolites in the medium from both the cyclooxygenase pathway (HHT, TXB2, and PGE2, in decreasing quantities, respectively) and the lipoxygenase pathway (LTB4, 5-HETE, 12-HETE, and LTC4). The major product was LTB4. Treatment of the macrophages with asbestos fibers induced the release of a similar array of AA metabolites, although there were smaller amounts of LTC4 and 12-HETE, but increased quantities of PGF2 alpha. A time course study showed a steady increase in metabolite production for 1 h, followed by a plateau. In addition, the amount of metabolites released was dependent on asbestos concentrations. Phagocytosis of iron beads induced the secretion of the same metabolites as asbestos stimulation, but in larger quantities, probably reflecting the lack of cytotoxicity of the particle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2003

Asbestos inhalation induces tyrosine nitration associated with extracellular signal-regulated kinase 1/2 activation in the rat lung.

Nitration of proteins by peroxynitrite (ONOO-) has been shown to critically alter protein function in vitro. We have shown previously that asbestos inhalation induced nitrotyrosine formation, a marker of ONOO- production, in the rat lung. To determine whether asbestos-induced protein nitration may affect mitogen-activated protein kinase (MAPK) signaling pathways, lung lysates from crocidolite and chrysotile asbestos-exposed rats and from sham-exposed rats were immunoprecipitated with anti-nitrotyrosine antibody, and captured proteins were subjected to Western blotting with anti-phospho-extracellular signal-regulated kinase (ERK)1/2 antibodies. Both types of asbestos inhalation induced significantly greater phosphorylation of ERK1/2 in rat lung lysates than was noted after sham exposure. Phosphorylated ERK proteins co-immunoprecipitated with nitrotyrosine. Moreover, in MAPK functional assays using Elk-1 substrate, immunoprecipitated phospho-ERK1/2 in lung lysates from both crocidolite-exposed and chrysotile-exposed rats demonstrated significantly greater phosphorylation of Elk-1 than was noted after sham exposure. Asbestos inhalation also induced ERK phosphorylation in bronchoalveolar lavage cells. Lung sections from rats exposed to crocidolite or chrysotile (but not from sham-exposed rats nor from rats exposed to "inert" carbonyl iron particles) demonstrated strong immunoreactivity for nitrotyrosine and phospho-ERK1/2 in alveolar macrophages and bronchiolar epithelium. These findings suggest that asbestos fibers may activate the ERK signaling pathway by generating ONOO- or other nitrating species that induce tyrosine nitration and phosphorylation of critical signaling molecules.

Animals↗