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PubMed2000

Analysis of K-ras and p53 mutations in mesotheliomas from humans and rats exposed to asbestos.

Malignant mesothelioma is known to be associated with asbestos exposure. However, the mechanism of mesothelial carcinogenesis in relation to the activation of proto-oncogenes or inactivation of tumor suppressor genes remains unclear. In this study, the PCR-Primer Introduced Restriction Site (PCR-PIRS) assay was employed to examine mutations in the K-ras proto-oncogene in mesothelioma tissues from workers exposed to asbestos and from rats treated with asbestos. Mutations in exons 5-8 of the p53 tumor suppressor gene were determined by direct DNA sequence analysis. Results of the PCR-PIRS analysis revealed no mutations in codons 12, 13 or 61 of the K-ras gene in any of the 17 human or 22 rat mesothelioma tissue samples. These results were confirmed by direct DNA sequence analysis. No mutations were found in exons 5-8 of the p53 gene in any of the mesothelioma tissue samples analyzed. These results and the results reported by others indicate that the K-ras proto-oncogene and p53 tumor suppressor gene may not play a critical role in the induction of mesothelioma by asbestos either in humans or in rats.

Animals↗

PubMed2004

Reconstruction of a century of airborne asbestos concentrations.

Airborne asbestos concentrations have been reconstructed for the entire 20th century for the first time through a combination of paleolimnological methods, particle-separation techniques, and analytical transmission electron microscopy. Pb concentrations and respirable aerosol mass concentrations in air and sediments yielded collection efficiencies of approximately 3000 m3 of air per gram of lake sediment. Airborne concentrations of chrysotile, the most common type of asbestos, reconstructed from control lake sediments echoed chrysotile's usage during the 20th century, with the highest concentrations mid-century (approximately 0.1 fibers/cm3) and then decreasing in the last quarter century. Reconstructed airborne concentrations of anthophyllite asbestos, a byproduct of local talc mining and milling, increased from <0.004 to 0.022 fibers/cm3 from 1846 to 1967. These anthophyllite concentrations during the approximately 100-year period of talc mining correlated well (r2 = 0.80, p < 0.01) with annual production of local talc and were much higher (p = 0.004) than concurrent concentrations in a control lake located upwind of the mines and mills. All of the chrysotile and more than 70% of the anthophyllite asbestos fibers were too narrow to be detected by phase-contrast light microscopy, the method used to measure airborne fiber concentrations before approximately 1980.

Air Pollutants↗

PubMed2001

Information about occupational exposure to asbestos given to cases in an etiological study: ethical aspects.

The aim of the study is to consider some ethical aspects of the provision of information, to the cases or their families, about the assessment of occupational asbestos exposure obtained in a case-control study of malignant mesothelioma of the pleura. An informative letter with the result of the evaluation of their occupational exposure to asbestos was sent to the participating cases (and/or their family). Those whose exposure was classified as certain/probable were also informed of the legislation regarding occupational diseases. Of the 132 cases, 32.6% of subjects and/or their families made telephone calls expressing interest in the content of the informative letter. Among the 63 cases classified as certain/probable exposure, this proportion was 47.6%. Out of 43 cases in which the age at diagnosis was < or = 65 years and the exposure to asbestos was certain/probable, only two (4.6%) were signed off work owing to occupational disease. Only one of the mesothelioma cases was recognized by the Spanish National Institute for Social Security (INSS) as having an occupational disease. The process of communication of the results of an epidemiological research should include the provision of information on the exposure data to each one of the subjects, and/or their families. There is a great disparity between the number of cases of certain/probable exposure to asbestos identified in our study, and the number registered as an occupational disease by the INSS.

Asbestos↗

PubMed2002

The molecular epidemiology of asbestos and tobacco in lung cancer.

Asbestos is a well-known toxin and lung carcinogen. Epidemiologic studies have established tobacco smoke and asbestos exposures synergistically interact to enhance lung cancer risk. The biologic mechanism responsible for this interaction has been the subject of considerable debate. Studies have suggested that asbestos may act as a carcinogen by generating free radical and reactive oxygen species, by inducing tissue injury and subsequent cellular growth, via large-scale chromosome loss and by enhancing delivery of tobacco carcinogens to the respiratory epithelium. Recent molecular epidemiologic approaches further suggest that asbestos enhances the mutagenicity of tobacco carcinogens and that it acts, at least in part, independent of the tissue damage responsible for fibrosis.

Asbestos↗

PubMed2003

Hemizygosity of Nf2 is associated with increased susceptibility to asbestos-induced peritoneal tumours.

Biallelic NF2 gene inactivation is frequently found in human malignant mesothelioma. In order to assess whether NF2 hemizygosity may enhance susceptibility to asbestos fibres, we investigated the Nf2 status in mesothelioma developed in mice presenting a heterozygous mutation of the Nf2 gene (Nf2(KO3/+)), after intraperitoneal inoculation of crocidolite fibres. Asbestos-exposed Nf2(KO3/+) mice developed tumoural ascites and mesothelioma at a higher frequency than their wild-type (WT) counterparts (P&<0.05). Six out of seven mesothelioma cell lines established from neoplastic ascitic fluids of Nf2(KO3/+) mice exhibited loss of the WT Nf2 allele and no neurofibromatosis type 2 protein expression was found in these cells. The results show the importance of the NF2 gene in mesothelial oncogenesis, the potential association of asbestos exposure and tumour suppressor gene inactivation, and suggest that NF2 gene mutation may be a susceptibility factor to asbestos.

Animals↗

PubMed2004

Cell type-specific effects of asbestos on intracellular ROS levels, DNA oxidation and G1 cell cycle checkpoint.

Exposure to asbestos fibers increases the risk of development of mesotheliomas and lung carcinomas, but not fibrosarcomas. We present data suggesting that resistance of fibroblasts to asbestos-induced carcinogenesis is likely to be connected with their lower ability to generate reactive oxygen species (ROS) in response to asbestos exposure and stricter control of proliferation of cells bearing asbestos/ROS-induced injuries. In fact, chrysotile (Mg6Si4O10(OH)8) asbestos exposure (5-10 microg/cm2) increased intracellular ROS and 8-oxo-guanine contents in rat pleural mesothelial cells, but not in lung fibroblasts. Simultaneously, moderate dosages of chrysotile and other agents increasing ROS levels (hydrogen peroxide, H2O2 and ethyl-methanesulfonate, EMS) inhibited cell cycle progression, in particular G1-to-S transition, in fibroblasts, but not in mesothelial cells. The arrested fibroblasts underwent cell death, while the majority of chrysotile-treated mesothelial cells survived. The differences in cell cycle response to asbestos/ROS-induced injuries correlated with distinct activity of p53-p21Cip1/Waf1 pathway in the two cell types. Chrysotile, H2O2 and EMS caused p53 upregulation in both cell types, but mesothelial cells, unlike fibroblasts, showed no accumulation of p21Cip1/Waf1. Of note, treatment with doxorubicin caused similar p53-dependent p21Cip1/Waf1 upregulation and cell cycle arrest in both cell types. This suggests differential response of fibroblasts and mesothelial cells specifically to asbestos/ROS exposure rather than to all DNA-damaging insults.

Animals↗

PubMed2000

Asbestos-related benign pleural disease.

Benign pleural disease is the commonest manifestation of asbestos exposure encountered by radiologists. Benign pleural thickening can appear as circumscribed parietal pleural plaques or as more diffuse thickening of the visceral pleura. Benign-asbestos induced pleural effusions are a significant and under-recognized manifestation of asbestos exposure with important sequelae, such as diffuse pleural thickening which may be associated with functional impairment and for which compensation may be sought. This review concentrates on the strengths and weaknesses of chest radiography and computed tomography for the detection and characterization of benign asbestos-related pleural disease and the relevance of imaging abnormalities to compensation and functional impairment.Peacock, C. (2000). Clinical Radiology55, 422-432.

Asbestos↗

PubMed2001

[Asbestos-induced malignant mesothelioma of the tunica vaginalis testis].

Since 1977 the diffuse malignant mesothelioma of the pleura and peritoneum caused by asbestos represents one of the most often compensated occupational cancers in Germany. Because of the probability of an asbestos-related etiology, it is considered as a "signal tumour", mainly indicating exposure to asbestos dust at the workplace. Two cases of histologically confirmed rare malignant mesothelioma of the tunica vaginalis testis are presented. Previous exposure to asbestos at the workplace is to be considered as a causal factor in both tumors. If cases of mesothelioma occur the criteria for indicating an occupational disease (No. 4105 of the German Law of Occupational Diseases, BKV) are fulfilled.

Aged↗

PubMed2000

Scanning electron microscopical investigations of broncho-alveolar casts after intratracheal asbestos fibre instillation.

The evaluation of the toxicity of mineral fibres has been tried to achieve in experimental animal models. However, the appearance of fibres in the pleural space could not be explained satisfactorily. Histomorphological examinations showed that intratracheal instillation of asbestos fibres leads to parabronchial and intraalveolar granulomatous tissue reactions and bronchial epithelial regenerations. For further elucidation of the pathogenesis of lung cancer and of mesothelioma the localisation and transport of inhaled fibres is of high interest. Thus, a three dimensional visualization of the structure of rat lungs before and after intratracheal instillation of UICC crocidolite fibres was performed by plastic casts to follow the way of asbestos fibres in the lung tissues and the pleura. The casts allowed to demonstrate airway structures with imprints of epithelial cells and blood vessels of normal and treated animals by scanning electron microscopy. Instilled asbestos fibres transformed bronchial structures and resulted in cystic deformations of the pleural surface. The penetration of single fibres through bronchial trunks and the visceral pleura could be shown for the first time in a three-dimensional topography of the affected tissue. Now, there is support for similar results of histomorphological examinations indicating the possibility that asbestos fibres could penetrate the pleura and migrate into the pleural space. The question if the migration of fibres is a mechanical movement or an active transport is still under discussion.

Animals↗

PubMed1975

Calibration standards for counting asbestos.

A laboratory proficiency testing program has been initiated by NIOSH to permit standardization of asbestos counting procedures by various state agencies. This has required preparation of multiple membrane filter samples containing "identical and predictable" concentrations of asbestos fibers, with consistent particulate backgrounds. A technique to filter liquid (toluene) suspensions was developed to provide chrysotile asbestos standards ranging from 200 to 1,500 fibers/mm-2 of filter area, with an aluminum oxide particulate background. Details of the necessary techniques are described. To evaluate variations inherent in preparing these "identical" samples and to estimate variations between different counters, extensive replicate fiber counting was performed. Count data from several counters at a single facility show that this liquid suspension filtration technique provides reproducible asbestos standards as measured by optical microscopy with a coefficient of variation of plus or minus 20% with the maximum individual variations of plus or minus 50%.

Air Pollution↗

PubMed1975

Physical parameters of airborne asbestos fibres in various work environments-preliminary findings.

The results of a pilot investigation to describe the physical parameters, length, aspect ratio, mass and shape of airborne fibres in a variety of industries producing processing and handling chrysotile, amosite and crocidolite are described. Samples of airborne dust were collected on nucleopore membrane filters and examined by scanning electron microscopy. The diameters and lengths of airborne fibres collected during the dumping of raw amosite at an asbestos products plant were greater than those of fibres collected during the application of amosite insulation. Chrysotile fibres collected in the carding area of an asbestos textile plant also tended to have smaller diameters than fibres collected in the dryer and bagging areas of an asbestos mill. The measurements of fibre dimensions indicate that the degree of protection afforded a worker by optical counts using the membrane filter technique is likely to depend on variety of asbestos and stage of processing. Preliminary results are not in conflict with experimental data suggesting that asbestosis might be related to the mass of airborne dust and primary malignant mesothelial tumors to exposure to fibres in a specific range of fibre diameter and length.

Air Pollutants↗

PubMedDate not supplied

Cancer mortality in relation to asbestos in municipal water supplies.

The mortality experience of twenty-two municipalities in Quebec grouped by evidence of exposure to asbestos fibers in water supplies (known high, possible high, and probable low exposures) was evaluated. Excess mortality due to cancer of the stomach (males), pancreas (females), and lung (males) was observed in the two municipalities with known high exposures. The excesses among males have been due to occupational exposure to asbestos. The absence of excess mortality due to pancreatic cancer among males suggested that the excess among females was not due to waterborne asbestos. The study therefore did not reveal evidence of excess cancer mortality that could be attributed to exposure to asbestos in drinking water.

Adult↗

PubMedDate not supplied

The Tyler Asbestos Workers Program. I. A medical surveillance model and method.

An asbestos-exposed worker who smokes cigarettes has a high risk of developing cancer of the lung. One thousand ninety-five former workers at a plant manufacturing asbestos (amosite) insulation products were exposed to high levels of asbestos dust concentrations in the atmosphere. The workers have been identified and located. A semi-annual medical surveillance program has been developed with National Cancer Institute support. Examination of the worker includes the following: history (questionnaire), physical examination, sputum cytopathology, chest roentgenogram, pulmonary function studies, and other tests. Emphasis has been placed on understanding the role of sputum cytopathology in a cancer control program in former asbestos workers.

Adult↗

PubMedDate not supplied

Epidemiologic investigation of respiratory effects related to environmental exposure to asbestos inside insulated buildings.

The respiratory effects of environmental pollution by asbestos inside university buildings were studied by comparing radiographic, clinical, and functional parameters among three groups of workers with different levels of exposure. Eight hundred and twenty-eight (828) people who worked for at least 15 yr in asbestos-insulated buildings and who were without known occupational exposure to asbestos (environmentally exposed group [EE]) were compared to a group of 252 workers with occupational exposure (occupationally exposed group [OE]), used as positive control; and to a group of 350 people with no known exposure to asbestos (nonexposed group [NE]), within the same university. After adjustment for confounding variables, no differences could be seen between groups EE and NE. Group OE exhibited a higher prevalence of pleural changes and lower lung functions than groups EE and NE.

Adult↗

PubMedDate not supplied

Radiological abnormalities among sheet-metal workers in the construction industry in the United States and Canada: relationship to asbestos exposure.

We investigated the possible adverse health effects to sheet-metal workers who had past exposure to asbestos. A cross-sectional medical examination of 1,330 workers was conducted during 1986 and 1987 in seven cities in the United States and Canada. A total of 1,016 workers had been employed for at least 35 y in the industry, and the mean duration from onset of asbestos exposure was 39.5 y (SD = 7.41 y). Chest x-ray abnormalities were found in more than half of the group. Pleural fibrosis, the most frequently found abnormality, was present in 47.0% of the cases and was the only abnormality found in 27.8% of cases; parenchymal interstitial fibrosis, found in 33.1% of cases, was the only abnormality found in 16.2% of cases. Radiologic abnormalities increased as duration of exposure increased. A positive smoking history was associated with a higher prevalence of radiologically detectable parenchymal abnormalities, a finding confirmed by us and others. Dyspnea on exertion was graded by a Medical Research Council questionnaire, the examinee's self-assessment, and a more detailed 12-point scale questionnaire. Few persons had marked shortness of breath, and approximately one-third had slight dyspnea. Individuals who had radiologic abnormalities experienced more shortness of breath than did those who had no radiologic abnormalities. Cigarette smoking also resulted in a higher prevalence of dyspnea. The results indicate that during the past, construction sheet-metal workers have been significantly exposed to asbestos on the job. Every effort should be made to minimize the anticipated serious health consequences, and further asbestos exposure for those who continue in this trade should be avoided.

Adult↗

PubMed2001

Chrysotile asbestos fibers detected in the newborn pups following gavage feeding of pregnant mice.

Female pregnant mice were fed chrysotile asbestos suspension by gavage to determine whether there is transfer of fibers to the fetuses. Groups of mice were given 2 doses of either 50 microg chrysotile suspension in 0.2 ml sterile normal saline (treated), or 0.2 ml saline (control), and were allowed to mate 2 d later. After pregnancy was confirmed, the treated and control groups received 2 additional doses of chrysotile asbestos or saline on gestational d 7 and 12. Both groups were allowed to deliver naturally, and the pups were sacrificed at 8, 1, 19, or 20 d after birth. The lungs and liver of two pups from each mother were processed for fiber counts using electron microscopy and energy-dispersive x-ray analysis (EDXA). All pups of the treated group had chrysotile fibers, while none were present in pups from controls. The mean fiber count of the lungs of treated group of pups was 780 fibers/g, and the mean fiber count of the liver was 214 fibers/g. Mean length of the fibers in the lung and liver was 18.48 microm and 18.30 microm, respectively. The fibers were thin, measuring 0.42 microm and 0.33 microm in the lung and liver, respectively. There was no significant difference in the weight gain between the treated and control group of pups. The postnatal fetal mortality of the 2 groups, 8.2% for the treated and 4.5% for the control group, were not statistically significant. To our knowledge, this is the first animal study to demonstrate that oral ingestion of chrysotile asbestos during pregnancy results in transfer of asbestos fibers to the fetuses.

Administration, Oral↗

PubMed1999

Role of iron in asbestos-body-induced oxidant radical generation.

Asbestos bodies (AB) were harvested from human lung tissue digests and isolated from uncoated asbestos fibers. Samples containing 1000 AB were added to a reactive solution to investigate the ability of AB to oxidize deoxy-D-ribose and generate reactive oxygen species (ROS) in the presence of ascorbate and hydrogen peroxide as determined by formation of thiobarbituric acid (TBA)-reactive products. Three types of asbestos fibers were tested for comparison, since they are known to be able to produce ROS. The absorbance values measured with 1000 AB were significantly higher than those observed with 1000 fibers of the three types of asbestos. Since in our reaction system the only source of transition metals was the iron-rich AB, data suggest iron derived from the ferritin coating of AB was involved in oxidant generation. Addition of iron to AB enhanced TBA-reactive product formation, while chelation of Fe with deferoxamine reduced this reaction. Hydroxyl radical scavengers 1,3-dimethyl-2-thiourea (DMTU) and mannitol (MN) also effectively blocked TBA-reactive product generation. Data indicate the importance of Fe in AB-induced oxidant damage. With the addition of polymorphonuclear leukocytes (PMN) to AB, incubation in the reactive solution gave very high amounts of TBA-reactive products, but using a reactive solution devoid of ascorbate, very low amounts of TBA-reactive products were generated. In the latter condition, the superoxide of cell membranes probably reduced and removed iron from AB-coating ferritin, but less effectively than ascorbate. Further after the possible reoxidation of Fe2+, Fe3+ could be coordinated by lactoferrin. Since such availability of reductant is never approached in living systems, the iron in the AB coating is unlikely to function as a catalyst of Fenton-type reactions in vivo.

Asbestos↗

PubMed2006

A review of scientific literature examining the mining history, geology, mineralogy, and amphibole asbestos health effects of the Rainy Creek igneous complex, Libby, Montana, USA.

This article reviews the past 90 yr of scientific research directed on multiple aspects of the unique geology and environmental health issues surrounding the vermiculite deposit found at Libby, MT. Hydrothermal alteration and extensive weathering of the ultramafic units resulted in the formation of a rich deposit of vermiculite that was mined for 67 yr and used in numerous consumer products in its expanded form. Later intrusions of alkaline units caused hydrothermal alteration of the pyroxenes, resulting in formation of amphiboles. Some of these amphiboles occur in the asbestiform habit and have been associated with pulmonary disease in former miners and mill workers. Identification of these amphibole asbestos minerals has received little attention in the past, but recent work shows that the majority of the amphibole mineral species present may not be any of the amphibole species currently regulated by government agencies. Epidemiological studies on former miners have, nevertheless, shown that the amphibole asbestos from the Rainy Creek igneous complex is harmful; also, a recent study by the Agency for Toxic Substances and Disease Registry shows that residents of Libby who had not been employed in the vermiculite mining or milling operations also appear to have developed asbestos-related pulmonary diseases at a higher rate than the general public elsewhere. Since November 1999, the U.S. Environmental Protection Agency has been involved in the cleanup of asbestos-contaminated sites in and around Libby associated with the mining and processing of vermiculite.

Aluminum Silicates↗