asbestos--crocidolite and Lung-Diseases

Scattered patches of crocidolite, one form of asbestos, were found in the surface soil in the rural county of Da-yao in southwestern China. In 1983, researchers from the West China University of Medical Sciences (WCUMS) discovered that residents of two villages in Da-yao had hyperendemic pleural plaques and excessive numbers of pleural mesotheliomas.. To review and summarise epidemiological studies, along with other relevant data, and to discuss the potential contribution to environmental risk assessment.. This report is based on a review of several clinical/epidemiological studies conducted by WCUMS researchers since 1984, which included one cross sectional medical examination survey, one clinical/pathological analysis of 46 cases of mesothelioma, and three retrospective cohort mortality studies. Additional information acquired from reviewing original data first hand during a personal visit along with an interview of medical specialists from Da-yao County Hospital was also incorporated.. The prevalence of pleural plaque was 20% among peasants in Da-yao over 40 years of age in the cross sectional survey. The average number of mesothelioma cases was 6.6 per year in the 1984-95 period and 22 per year in the 1996-99 period, in a population of 68 000. For those mesothelioma cases that were histology confirmed, there were 3.8 cases/year in the first period and 9 cases/year in the second. Of the 2175 peasants in this survey, 16 had asbestosis. Lung cancer deaths were significantly increased in all three cohort studies. The annual mortality rate for mesothelioma was 85 per million, 178 per million, and 365 per million for the three cohort studies, respectively. The higher exposed peasants had a fivefold increased mesothelioma mortality compared to their lower exposed counterparts. There were no cases of mesothelioma in the comparison groups where no crocidolite was known to exist in the environment. In the third cohort study, almost one of five cancer deaths (22%) was from mesothelioma. The ratio of lung cancer to mesothelioma deaths was low for all three studies (1.3, 3.0, and 1.2, respectively).. The observation of numerous mesothelioma cases at Da-yao was a unique finding, due mainly to their lifetime exposure to crocidolite asbestos. The finding of cases dying at a younger age and the relatively high ratio of mesothelioma cases to lung cancer could also be another unique result of lifetime environmental exposure to crocidolite asbestos. Although the commercial use of crocidolite has been officially banned since 1984, the incidence of mesothelioma has continued to show a steady increase, particularly among peasants. Since the latency of mesothelioma is approximately 30-40 years, the ban had little effect in the 1990s. The increased awareness and changes in diagnosis over time may also contribute to the increase. Furthermore, exposure to asbestos stoves and walls continued. The government implemented reduction of these exposures. However, from a public health standpoint, the most important issue is the complete avoidance of further exposure to asbestos.

Topics: Asbestos, Crocidolite; China; Cohort Studies; Environmental Exposure; Humans; Lung Diseases; Mesothelioma; Pleural Diseases; Residence Characteristics; Retrospective Studies; Risk Assessment; Soil

The final results from this multi-dose, 90-day inhalation toxicology study in the rat with life-time post-exposure observation have shown a significant fundamental difference in pathological response and tumorgenicity between brake dust generated from brake pads manufactured with chrysotile or from chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. The groups exposed to brake dust showed no significant pathological or tumorigenic response in the respiratory track compared to the air control group at exposure concentrations and deposited doses well above those at which humans have been exposed. Slight alveolar/interstitial macrophage accumulation of particles was noted. Wagner grades were 1-2 (1 = control group), similar to the TiO

Topics: Air Pollutants; Animals; Asbestos, Amosite; Asbestos, Crocidolite; Dose-Response Relationship, Drug; Lung; Lung Diseases; Microscopy, Confocal; Rats; Time Factors

Human exposure to asbestos can cause a wide variety of lung diseases that are still a current major health concern, even if asbestos has been banned in many countries. It has been shown in many studies that asbestos fibers, ingested by alveolar macrophages, disrupt lung iron homeostasis by sequestering iron. Calcium can also be deposited on the fibers. The pathways along which iron and above all calcium interact with fibers are still unknown. Our aim was that of investigating if the iron accumulation induced by the inhaled asbestos fibers also involves calcium ions accumulation. Lung sections of asbestos-exposed mice were analyzed using an extremely sensitive procedure available at the synchrotron facilities, that provides morphological and chemical information based on X-ray fluorescence microspectroscopy (μ-XRF). In this study we show that (1) where conventional histochemical procedures revealed only weak deposits of iron and calcium, μ-XRF analysis is able to detect significant deposits of both iron and calcium on the inhaled asbestos fibers; (2) the extent of the deposition of these ions is proportionally directly related and (3) iron and calcium deposition on inhaled asbestos fibers is concomitant with the appearance of inflammatory and hyperplastic reactions.

Topics: Animals; Asbestos, Crocidolite; Asbestosis; Calcium; Homeostasis; Humans; Inhalation Exposure; Iron; Lung; Lung Diseases; Macrophages, Alveolar; Male; Mice; Mice, Inbred C57BL; Microscopy; Microscopy, Fluorescence; Synchrotrons; Tissue Distribution; X-Rays; Zinc

Asbestos has been shown to cause chromosomal damage and DNA aberrations. Exposure to asbestos causes many lung diseases e.g. asbestosis, malignant mesothelioma, and lung cancer, but the disease-related processes are still largely unknown. We exposed the human cell lines A549, Beas-2B and Met5A to crocidolite asbestos and determined time-dependent gene expression profiles by using Affymetrix arrays. The hybridization data was analyzed by using an algorithm specifically designed for clustering of short time series expression data. A canonical correlation analysis was applied to identify correlations between the cell lines, and a Gene Ontology analysis method for the identification of enriched, differentially expressed biological processes.. We recognized a large number of previously known as well as new potential asbestos-associated genes and biological processes, and identified chromosomal regions enriched with genes potentially contributing to common responses to asbestos in these cell lines. These include genes such as the thioredoxin domain containing gene (TXNDC) and the potential tumor suppressor, BCL2/adenovirus E1B 19kD-interacting protein gene (BNIP3L), GO-terms such as "positive regulation of I-kappaB kinase/NF-kappaB cascade" and "positive regulation of transcription, DNA-dependent", and chromosomal regions such as 2p22, 9p13, and 14q21. We present the complete data sets as Additional files.. This study identifies several interesting targets for further investigation in relation to asbestos-associated diseases.

Topics: Asbestos, Crocidolite; Cell Line; Cluster Analysis; Epithelium; Gene Expression Profiling; Humans; Lung; Lung Diseases; Nucleic Acid Hybridization

Asbestosis is a chronic form of interstitial lung disease characterized by inflammation and fibrosis that results from the inhalation of asbestos fibers. Although the pathogenesis of asbestosis is poorly understood, reactive oxygen species may mediate the progression of this disease. The antioxidant enzyme extracellular superoxide dismutase (EC-SOD) can protect the lung against a variety of insults; however, its role in asbestosis is unknown. To determine if EC-SOD plays a direct role in protecting the lung from asbestos-induced injury, intratracheal injections of crocidolite were given to wild-type and ec-sod-null mice. Bronchoalveolar lavage fluid (BALF) from asbestos-treated ec-sod-null mice at 24 h, 14 days, or 28 days posttreatment showed increased inflammation and total BALF protein content compared to that of wild-type mice. In addition, lungs from ec-sod-null mice showed increased hydroxyproline content compared to those of wild-type mice, indicating a greater fibrotic response. Finally, lungs from ec-sod-null mice showed greater oxidative damage, as assessed by nitrotyrosine content compared to those of their wild-type counterparts. These results indicate that depletion of EC-SOD from the lung increases oxidative stress and injury in response to asbestos.

Topics: Animals; Asbestos, Crocidolite; Bronchoalveolar Lavage Fluid; Hydroxyproline; Inflammation; Lung; Lung Diseases; Lung Injury; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Superoxide Dismutase; Tyrosine

Exposure to asbestos and air pollution particles can be associated with increased human morbidity and mortality. However, the molecular mechanism of lung injuries remains unknown. It has been postulated that the in vivo toxicity results from the catalysis of free radical generation. Using electron spin resonance (ESR) in conjunction with the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) we previously investigated in vivo free radical production by rats treated with intratracheal instillation of asbestos (crocidolite fibers) and an emission source air pollution particle (oil fly ash). In this report we compare the effect of two different exposures on the type of free radicals they induce in in vivo animal model. Twenty-four hours after the exposure, ESR spectroscopy of the chloroform extract from lungs of animals exposed to either asbestos or oil fly ash gave a spectrum consistent with a carbon-centered radical adduct (aN = 15.01 G and aH = 2.46 G). To test whether free radical formation occurred in vivo and not in vitro, a number of control experiments were performed. Combinations (both individually and together) of asbestos or oil fly ash and 4-POBN were added to lung homogenate of unexposed rats prior to chloroform extraction. No detectable ESR signal resulted. To exclude the possibility of ex vivo free radical generation, asbestos or oil fly ash was added to lung homogenate of an animal treated with 4-POBN. Also, 4-POBN was added to lung homogenate from rats instilled with asbestos or oil fly ash. Neither system produced radical adducts, indicating that the ESR signal detected in the lung extracts of the treated animals must be produced in vivo and not ex vivo or in vitro. In conclusion, ESR analysis of lung tissue demonstrated that both exposures produce lipid-derived radical metabolites despite their different composition and structure. Analogously, both exposures provide evidence of in vivo enhanced lipid peroxidation. Furthermore, it is concluded that without the presence of a spin-trapping agent, no free radical metabolites could be detected directly by ESR in either exposure.

Topics: Air Pollutants; Animals; Asbestos, Crocidolite; Carbon; Carcinogens; Coal Ash; Electron Spin Resonance Spectroscopy; Free Radicals; Instillation, Drug; Lipid Peroxidation; Lung; Lung Diseases; Male; Oxidation-Reduction; Particle Size; Particulate Matter; Rats; Rats, Sprague-Dawley; Spin Trapping

Increased rates of death from asbestos related diseases have been reported in former workers and residents exposed to crocidolite (blue asbestos) at Wittenoom, Western Australia. Exposure to asbestos is associated with reduced static lung volumes, gas transfer and lung compliance, and a restrictive ventilatory abnormality.. The effects of crocidolite exposure and smoking history on levels and rates of change of lung function were evaluated using a linear mixed model. Lung function was measured as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC.. Cumulative doses of asbestos and the presence of radiographic asbestosis were associated with lower levels of FEV1 and FVC and a steeper decline during the period of observation. Subjects exposed to asbestos at a younger age had lower levels of FEV1 and FVC. Current smokers had lower levels and a steeper decline in lung function than never smokers. No significant interactions between crocidolite exposure and smoking on the levels or rates of change of lung function were found.. The deleterious effects of crocidolite exposure on lung function persist in this population, despite asbestos exposure having ceased more than 30 years ago. No significant interactions were found in this population between asbestos and smoking at the first visit or longitudinally.

Topics: Asbestos, Crocidolite; Asbestosis; Environmental Exposure; Female; Forced Expiratory Volume; Humans; Lung Diseases; Male; Middle Aged; Radiography; Regression Analysis; Smoking; Vital Capacity; Western Australia

It has been postulated that the in vivo toxicity of asbestos results from its catalysis of free radical generation. We examined in vivo radical production using electron spin resonance (ESR) coupled with the spin trap alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (4-POBN); 180 day-old rats were intratracheally instilled with either 500 microg crocidolite or saline. Twenty-four hours later, histologic examination revealed a neutrophilic inflammatory response. ESR spectroscopy of the chloroform extract from lungs exposed to asbestos gave a spectrum consistent with a carbon-centered radical adduct, while those spectra from lungs instilled with saline revealed a much weaker signal. This same radical formation persisted and, even one month after instillation, could be detected in the lungs of rats exposed to asbestos. The 4-POBN adducts detected by ESR are very similar to, if not identical with, ethyl and pentyl radical adducts, providing evidence of in vivo lipid peroxidation resulting from asbestos exposure. We conclude that, after instillation of crocidolite in the rat, ESR analysis of lung tissue demonstrates in vivo free radical production.

Topics: Animals; Asbestos, Crocidolite; Carcinogens; Catalysis; Electron Spin Resonance Spectroscopy; Free Radicals; Instillation, Drug; Lung Diseases; Male; Nitrogen Oxides; Pyridines; Rats; Rats, Sprague-Dawley; Spin Labels; Spin Trapping

Topics: Alkaline Phosphatase; Animals; Asbestos, Crocidolite; Bronchoalveolar Lavage Fluid; Calcium Sulfate; Cell Survival; Epithelium; gamma-Glutamyltransferase; Glutathione; In Vitro Techniques; Lung; Lung Diseases; Macrophages; Male; Mineral Fibers; Rats; Rats, Inbred F344

Nuclear factor kappa B (NF-kappa B) is a transcription factor regulating expression of genes intrinsic to inflammation and cell proliferation--features of asbestos-associated diseases. In studies here, crocidolite asbestos caused protracted and dose-responsive increases in proteins binding to nuclear NF-kappa B-binding DNA elements in hamster tracheal epithelial (HTE) cells. This binding was modulated by cellular glutathione levels. Antibodies recognizing p65 and p50 protein members of the NF-kappa B family revealed these proteins in two of the DNA complexes. Transient transfection assays with a construct containing six NF-kappa B-binding DNA consensus sites linked to a luciferase reporter gene indicated that asbestos induced transcriptional activation of NF-kappa B-dependent genes, an observation that was confirmed by northern blot analyses for c-myc mRNA levels in HTE cells. Studies suggest that NF-kappa B induction by asbestos is a key event in regulation of multiple genes involved in the pathogenesis of asbestos-related lung cancers.

Topics: Animals; Asbestos, Crocidolite; Cells, Cultured; Cricetinae; DNA; Epithelial Cells; Epithelium; Gene Expression Regulation; Genes, jun; Genes, myc; Glutathione; Lung Diseases; NF-kappa B; Promoter Regions, Genetic; Trachea

Urinary recovery of intratracheally instilled polyethylene glycol polymers (PEG:s) in the molecular weight range 722-1294 Da (PEG 1000) was studied under normal conditions and during experimentally induced lung damage in rats. The urinary PEG recoveries were between 30-60% under normal conditions, with a selectivity for smaller PEG:s. No significant differences in the urinary PEG molecular weight profiles were found between 30 days old and adult rats; i.e. they had similar PEG 1162/810 (molecular weights) urinary recovery ratios (0.78 +/- 0.25 and 0.69 +/- 0.27, respectively, p > 0.05). In rats instilled with PEG 1000 and ferritin (5 mg.kg-1 body weight), the urinary recovery was increased for PEG:s with molecular weights greater than 1030 Da; i.e. a higher PEG 1162/810 recovery ratio (1.44 +/- 0.58, p < 0.01) was obtained. Rats instilled with PEG 1000 and crocidolite asbestos fibres (5 mg.kg-1 body weight) showed higher urinary recoveries for PEG:s greater than 854 Da, resulting in a higher PEG 1162/810 ratio (1.47 +/- 0.59, p < 0.01). By adding the iron-chelator, desferrioxamine, to the crocidolite-instillate, the urinary recoveries and the PEG 1162/810 ratio (0.97 +/- 0.47) were reduced, indicating a restored molecular weight selectivity of the lung. Thus, in rats, PEG 1000 passes via the respiratory tract in large amounts which is dependent on the molecular weight. This passage was increased after ferritin- or crocidolite instillation, indicating that the barrier function of the respiratory tract was impaired due to local tissue damage, and that iron may play an important role in this.

Topics: Aging; Animals; Asbestos; Asbestos, Crocidolite; Asbestosis; Blood-Air Barrier; Ferritins; Instillation, Drug; Lung Diseases; Molecular Weight; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Trachea

Asbestos fibers adsorb cytochrome P-450 and P-448 proteins from rat lung micosomal fractions and liberate heme from cytochrome P-448 on prolonged incubation in vitro. further, fibers, decrease the activities of benzo(a)pyrene hydroxylase and glutathione-S-transferase in microsomal and cytosolic fractions respectively. Mineral fibers also stimulate both the enzymatic (NADPH-induced) and non-enzymatic (Fe2(+)-induced) lipid peroxidation in microsomal fractions. Preincubation of microsomal and cytosolic fractions with a physiological concentration of ascorbic acid ameliorates, to a large extent, the changes induced by asbestos fibers.

Topics: Animals; Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Ascorbic Acid; Cytochrome P-450 CYP1A2; Cytochrome P-450 Enzyme System; Cytochromes; Female; Lipid Peroxidation; Lung; Lung Diseases; Microsomes; Rats

The lungs from 36 former workers at an East London asbestos factory dying of asbestos-related disease were compared with lung tissue from 56 matched control patients operated on in East London for carcinoma of the lung. The severity of asbestosis and the presence of pulmonary carcinoma or mesothelioma of the pleura or peritoneum were correlated with an asbestos exposure index and with the type and amount of mineral fibre of the lungs. Asbestosis was associated with far heavier fibre burdens than mesothelioma. Moderate or severe asbestosis was more common among those with carcinoma of the lung than in those with mesothelial tumours. Crocidolite and amosite asbestos were strongly associated with asbestosis, carcinoma of the lung and mesothelial tumours, whereas no such correlation was evident with chrysotile or mullite. It is suggested that greater emphasis should be placed on the biological differences between amphibole and serpentine asbestos fibre.

Topics: Aluminum Silicates; Asbestos; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Female; Humans; London; Lung; Lung Diseases; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Occupational Diseases; Pleural Neoplasms

Fibrogenous effects of wollastonite, chrysotile and crocidolite have been investigated in experiments on animals. (Wollastonite is a calcium silicate of fibrous structure, occasionally applied as asbestos substitute). The experimental animals were intratracheally administered single doses of 50 mg of the test material suspended in 0.6 ml of physiological NaCl solution. The animals were decapitated 3, 6 and 9 months after the experiment. Fibrogenic properties were evaluated basing on the weight of wet lungs, content of lipids and hydroxyproline in lungs, as well as histopathological tests of lungs, mediastinal lymph nodes and spleen. Histopathological preparations were evaluated using an optical, microscope or transmission electron microscope. The findings of biochemical, pathomorphological, and ultrastructural studies demonstrated slight fibrogenic effects of wollastonite, as compared to chrysotile and crocidolite.

Topics: Animals; Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Calcium Compounds; Granuloma; Lung; Lung Diseases; Lymph Nodes; Male; Rats; Rats, Inbred Strains; Silicates; Silicic Acid; Silicon Dioxide

The relative in vitro and in vivo toxicity of several types of manufactured fibrous glass insulation and crocidolite asbestos was investigated to aid in selection of a suitable glass fiber for subsequent use in inhalation exposures. The in vitro cytotoxicity to pulmonary alveolar macrophages of small glass fibers from microfiber insulation (count median diameter (CMD) approximately 0.1-0.2 micrometer) was greater than that of the larger fibers from household insulation (CMD approximately 2.4 micrometers). To screen for in vivo pulmonary toxicity, 2-21 mg of glass or asbestos fibers were administered in divided doses to male Syrian hamsters by intratracheal instillation. Animals were sacrificed at 1, 3.5 and 11 months following initial administration of material. One type of glass microfiber [count median diameter (CMD) approximately 0.1 micrometer] caused deaths from pulmonary edema at early times after instillation. High levels of asbestos, a second glass microfiber (CMD approximately 0.2 micrometer) and one type of household insulation fiber (CMD 2.3 micrometers) all resulted in increase in total collagen and mild pulmonary fibrosis at later times after instillation, although microfiber insulation produced a greater response than household insulation. Asbestos insulation produced the greatest response. A five-day inhalation exposure to a high level of glass microfibers deposited in lung less than 10 percent of the lowest instilled amount which elicited indications of lung injury. This amount did not produce significant biological changes at 1 to 12 months after exposure.

Topics: Animals; Asbestos; Asbestos, Crocidolite; Construction Materials; Cricetinae; Environmental Exposure; Glass; Lung Diseases; Macrophages; Male; Mesocricetus; Pulmonary Alveoli; Pulmonary Edema; Pulmonary Fibrosis