Amphibole Asbestos Exposure Research Articles

Final results from a 90-day quantitative inhalation toxicology study evaluating the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos: Histopathological examination, confocal microscopy and collagen quantification of the lung and pleural cavity

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 TiO2 particle control group.Chrysotile was not biopersistent, exhibiting in the lung a deterioration of its matrix which results in breakage into particles and short fibers which can be cleared by alveolar macrophages and which can continue to dissolve. Particle-laden macrophage accumulation was observed, leading to a very-slight interstitial inflammatory response (Wagner grade 1–3). There was no peribronchiolar inflammation, occasional very-slight interstitial fibrosis (Wagner grade 4), and no exposure-related tumorigenic response.The pathological response of crocidolite and amosite compared to the brake dust and chrysotile was clearly differentiated by the histopathology and the confocal analysis. Crocidolite and amosite induced persistent inflammation, microgranulomas, persistent fibrosis (Wagner grades 4), and a dose-related lung tumor response. Confocal microscopy quantified extensive inflammatory response and collagen development in the lung, visceral and parietal pleura as well as pleural adhesions.These results provide a clear foundation for differentiating the innocuous effects of brake dust exposure from the adverse effects following amphibole asbestos exposure.

Evaluation of the exposure, dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study – Interim results Part 1: Experimental design, aerosol exposure, lung burdens and BAL

This 90-day repeated-dose inhalation toxicology study of brake-dust (BD) (brakes manufactured with chrysotile) in rats provides a comprehensive understanding of the biokinetics and potential toxicology in the lung and pleura. Exposure was 6 h/d, 5d/wk., 13wks followed by lifetime observation (~20 % survival). Control groups included a particle control (TiO2), chrysotile, commercial crocidolite and amosite asbestos.Aerosol fiber distributions of the chrysotile, crocidolite and amosite were similar (fibers L > 20 μm/cm3: chrysotile-Low/High 29/72; crocidolite 24; amosite 47 fibers/cm3; WHO-fibers/cm3: chrysotile-Low/High 119/233; crocidolite 181; amosite 281 fibers/cm3). The number of particles/cm3 in the BD was similar to that in the chrysotile, crocidolite & amosite exposures (BD 470–715; chrysotile 495–614; crocidolite 415; amosite 417 particles/cm3).In the BD groups, few fibers L > 20 μm were observed in the lungs at the end of exposure and no fibers L > 20 μm at 90d post exposure. In the chrysotile groups, means of 204,000 and 290,000 fibers(L > 20 μm)/lung were measured at 89d. By 180d, means of 1 and 3.9 fibers were counted on the filter corresponding to 14,000 and 55,000 fibers(L > 20 μm)/lung.In the crocidolite and amosite groups mean lung concentrations were 9,055,000 and 11,645,000 fibers(L > 20 μm)/lung at 89d. At 180d the means remained similar with 8,026,000 and 11,591,000 fibers(L > 20 μm)/lung representing 10–13% of the total lung fibers.BAL determined the total number of macrophages, lymphocytes, neutrophils, eosinophils, epithelial-cells and IL-1 beta, TNF-alpha and TGF-beta. At the moderate aerosol concentrations used in this study, neutrophil counts increased ~5 fold in the amphibole asbestos exposure groups. All other groups and parameters showed no important differences at these exposure concentrations. The exposure and lung burden results provide a sound basis for assessing the potential toxicity of the brake dust in comparison to the TiO2 particle control and the chrysotile, crocidolite and amosite asbestos control groups. The BAL results provide an initial indication of the differential response. Part 2 presents the presentation and discussion of the histopathological and confocal microscopy findings in this study through 90 days post exposure.

Evaluation of the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study – Interim results Part 2: Histopathological examination, Confocal microscopy and collagen quantification of the lung and pleural cavity

The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos.In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group.Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1–3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis.The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces.The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.

Mesothelial cell autoantibodies upregulate transcription factors associated with fibrosis

Amphibole asbestos exposure is associated with the production of mesothelial cell autoantibodies (MCAA). These MCAA have been linked with pleural fibrotic disease in the asbestos exposed community of Libby, Montana, and induce collagen deposition by cultured mesothelial cells. However, the exact intracellular mechanism by which these autoantibodies cause an increase in collagen deposition remains unknown. This study sought to gain insight into the transcription factors involved in the collagen production after human mesothelial cells are exposed to MCAA. In this study, transcription factor activation profiles were generated from human mesothelial cells (Met5A) treated with serum from Libby subjects, and were compared to cells treated with serum cleared of IgG, and therefore containing no MCAA. Analysis of those profiles indicated C/EBP-beta and hypoxia inducible factor 1 alpha (HIF-1α) are significantly increased in the nucleus, indicating activation, due to MCAA exposure compared to controls. Inhibition of either of these transcription factors significantly reduced collagen 1 deposition by these cells following exposure to MCAA. These data suggest autoantibodies are directly involved in type I collagen deposition and may elucidate potential therapeutic targets for autoantibody mediated fibrosis.

HRCT/CT and associated spirometric effects of low Libby amphibole asbestos exposure.

Evaluate the relationship between cumulative fiber exposure and high-resolution or conventional chest computed tomography (HRCT/CT) changes and spirometry of workers with Libby amphibole asbestos exposure. Of the original 1980 cohort (n = 513), 431 were living and asked to participate. Images were evaluated for localized pleural thickening (LPT), diffuse pleural thickening (DPT), and parenchymal changes. A total of 306 participants provided either HRCT/CT scans (n = 191) or chest radiographs (n = 115). Of the 191 with HRCT/CT, 52.9% had pleural changes and 13.1% had parenchymal changes. Those with LPT only, LPT and/or DPT, or DPT and/or parenchymal changes had mean 6.1, 8.0, and 18.0 loss in percent predicted forced vital capacity, respectively. Exposure to vermiculite containing amphibole fibers is associated with pleural and parenchymal HRCT/CT changes at low cumulative fiber exposure; these changes are associated with spirometric decrements.

Social Support Functions During a Slowly-Evolving Environmental Disaster: The Case of Amphibole Asbestos Exposure in Libby, Montana

Previous research concluded that victims of rapid-onset natural disasters (e.g., hurricanes) receive and provide high levels of instrumental support. However, different kinds of disasters (natural or human caused [technological, environmental, intentional/terrorism], rapid or slow onset, short or long duration) may create different stressors and thus influence the types of social support most needed and provided. We explored social support functions during an ongoing “slowly-evolving environmental disaster” in Libby, Montana due to widespread exposure to amphibole asbestos. Analyses of focus groups and in-depth interviews focused on the relative salience of support functions (emotional, informational, instrumental, and spiritual) identified as needed or provided. Dominant themes emerged around each function. Results indicated that informational support is particularly salient in this type of disaster. Although not all community members had experienced the disaster’s health consequences (asbestos-related disease [ARD]), all had been affected by the disaster and had informational needs. The nature of those informational needs (e.g., medical vs. financial) varied based on experience with ARD. Experience with ARD was associated with awareness of disaster-related emotional and instrumental support needed or provided. Results have implications for future research on slowly-evolving environmental disasters and institutional and community responses to them.

A Case Study Exploring Research Communication and Engagement in a Rural Community Experiencing an Environmental Disaster

As a means to involve the public in research, the National Institutes of Health (NIH) established the Partners in Research Program and solicited research grant applications from academic/scientific institutions and community organizations that proposed to forge partnerships: (a) to study methods and strategies to engage and inform the public regarding health science, and (b) to increase scientists’ understanding of and outreach to the public in their research efforts (NIH Public Trust, 2007). In this article, we report on a study funded by the NIH Partners in Research Program, to understand the research milieu (knowledge, acceptance, and research participation) and communication preferences of rural people experiencing an environmental disaster from amphibole asbestos exposure.

Tumors that mimic asbestos-related mesothelioma: time to consider a genetics-based tumor registry?

The diagnosis of mesothelioma is not always straightforward, despite known immunohistochemical markers and other diagnostic techniques. One reason for the difficulty is that extrapleural tumors resembling mesothelioma may have several possible etiologies, especially in cases with no meaningful history of amphibole asbestos exposure. When the diagnosis of mesothelioma is based on histologic features alone, primary mesotheliomas may resemble various primary or metastatic cancers that have directly invaded the serosal membranes. Some of these metastatic malignancies, particularly carcinomas and sarcomas of the pleura, pericardium and peritoneum, may undergo desmoplastic reaction in the pleura, thereby mimicking mesothelioma, rather than the primary tumor. Encasement of the lung by direct spread or metastasis, termed pseudomesotheliomatous spread, occurs with several other primary cancer types, including certain late-stage tumors from genetic cancer syndromes exhibiting chromosomal instability. Although immunohistochemical staining patterns differentiate most carcinomas, lymphomas, and mestastatic sarcomas from mesotheliomas, specific genetic markers in tumor or somatic tissues have been recently identified that may also distinguish these tumor types from asbestos-related mesothelioma. A registry for genetic screening of mesothelioma cases would help lead to improvements in diagnostic criteria, prognostic accuracy and treatment efficacy, as well as improved estimates of primary mesothelioma incidence and of background rates of cancers unrelated to asbestos that might be otherwise mistaken for mesothelioma. This information would also help better define the dose-response relationships for mesothelioma and asbestos exposure, as well as other risk factors for mesothelioma and other mesenchymal or advanced metastatic tumors that may be indistinguishable by histology and staining characteristics.

The role of social toxicity in responses to a slowly-evolving environmental disaster: the case of amphibole asbestos exposure in Libby, Montana, USA.

Experiencing a disaster has significant negative effects on psychological adjustment. Case study accounts point to two consistent trends in slowly-evolving environmental disasters: (a) patterns of negative social dynamics, and (b) relatively worse psychological outcomes than in natural disasters. Researchers have begun to explicitly postulate that the social consequences of slowly-evolving environmental disasters (e.g., community conflict) have their own effects on victims' psychological outcomes. This study tested a model of the relationship between those social consequences and psychological adjustment of victims of a slowly-evolving environmental disaster, specifically those whose health has been compromised by the amphibole asbestos disaster in Libby, MT. Results indicate that experiencing greater community conflict about the disaster was associated with greater family conflict about the disaster which, in turn, was associated with greater social constraints on talking with others about their disease, both directly and indirectly through experiencing stigmatization. Experiencing greater social constraints was associated with worse psychological adjustment, both directly and indirectly through failed social support. Findings have implications for understanding pathways by which social responses create negative effects on mental health in slowly-evolving environmental disasters. These pathways suggest points for prevention and response (e.g., social support, stigmatization of victims) for communities experiencing slowly-evolving environmental disasters.

Effects of Libby Amphibole Asbestos Exposure on Two Models of Arthritis in The Lewis Rat

Epidemiological data suggest that occupational exposure to the amphibole-containing vermiculite in Libby, MT, was associated with increased risk for developing autoimmune diseases and had an odds ratio of 3.23 for developing rheumatoid arthritis (RA). The collagen-induced arthritis (CIA) and the peptidoglycan-polysaccharide (PG-PS) models of RA were employed to determine whether exposure to Libby amphibole (LA) induced a more rapid onset, increased expression, or prolonged course of RA. Female Lewis rats were intratracheally instilled with total doses of 0.15, 0.5, 1.5, or 5 mg LA or 0.5 or 1.5 mg amosite asbestos, and arthritis was induced with either the PG-PS or CIA model. Neither LA nor amosite exposure affected the disease course in the CIA model, or the production of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibodies. LA exposure reduced swelling in the PG-PS model and decreased anti-PG-PS and total immunoglobulin M (IgM) antibody titers. Both amosite and LA exposure increased the number of rats with circulating anti-nuclear antibodies (ANA), the majority of which presented a speckled staining pattern. However, this ANA enhancement was not dose responsive. These results failed to show a positive correlation between LA exposure and RA disease in two animal models, although upregulated ANA suggest an altered immunological profile consistent with other systemic autoimmune diseases.

Mesothelial cell and anti-nuclear autoantibodies associated with pleural abnormalities in an asbestos exposed population of Libby MT

Despite data linking amphibole asbestos exposure with production of autoantibodies, the role of autoantibodies in subsequent disease is unknown. Residents of Libby, Montana have experienced significant exposure to amphibole asbestos due to the mining of asbestos-contaminated vermiculite near the community over several decades. This population predominantly exhibits pleural disease, and an autoimmune-like disorder that has yet to be well defined. This study sought to determine whether autoantibodies from asbestos-exposed subjects were associated with pleural lesions. Serum samples of subjects from Libby were evaluated for anti-nuclear antibodies (ANA) and mesothelial cell autoantibodies (MCAA) using cell based ELISA. The presence of radiographic abnormalities detected during the time frame of serum collection was determined from screening records. In accord with previous studies, 61.3% (76/124) of the Libby samples were ANA positive, a frequency much higher than expected for a healthy population. The odds of having pleural or interstitial abnormalities in Libby was nearly 3.55 times greater for individuals that tested positive for ANA compared with individuals negative for ANA ( p = 0.004). MCAA were also detected at a strikingly high frequency (18.5%; 23/124) in samples from Libby. Individuals with MCAA had 4.9 times the risk of having pleural abnormalities compared to MCAA-negative subjects ( p = 0.044). In conclusion, ANA and MCAA were elevated in a study population that was known to have chronic exposure to asbestos, and these autoantibodies were associated with pleural abnormalities, the predominant finding in the asbestos-exposed population of Libby. Additional research is needed to determine the role these autoantibodies may play in pulmonary disease.

Community‐Level Social Support Responses in a Slow‐Motion Technological Disaster: The Case of Libby, Montana

Social support is an important resource for communities experiencing disasters. However, a disaster's nature (rapid- versus slow-onset, natural versus technological) may influence community-level responses. Disaster research on social support focuses primarily on rapid-onset natural disasters and, to a lesser extent, rapid-onset technological disasters. Little research has addressed slow-onset disasters. This study explores social support processes in Libby, MT, a community experiencing a "slow-motion technological disaster" due to widespread amphibole asbestos exposure. A comprehensive social support coding system was applied to focus-group and in-depth-interview transcripts. Results reveal that, although the community has a history of normative supportiveness during community and individual crises, that norm has been violated in the asbestos disaster context. Results are interpreted as a failure to achieve an "emergent altruistic community." Specifically, community-level conflict appears to interfere with previously established social support patterns. The observed phenomenon can be understood as the deterioration of a previously supportive community.

Update of Potency Factors for Asbestos-Related Lung Cancer and Mesothelioma

The most recent update of the U.S. Environmental Protection Agency (EPA) health assessment document for asbestos (Nicholson, 1986, referred to as "the EPA 1986 update") is now 20 years old. That document contains estimates of "potency factors" for asbestos in causing lung cancer (K(L)'s) and mesothelioma (K(M)'s) derived by fitting mathematical models to data from studies of occupational cohorts. The present paper provides a parallel analysis that incorporates data from studies published since the EPA 1986 update. The EPA lung cancer model assumes that the relative risk varies linearly with cumulative exposure lagged 10 years. This implies that the relative risk remains constant after 10 years from last exposure. The EPA mesothelioma model predicts that the mortality rate from mesothelioma increases linearly with the intensity of exposure and, for a given intensity, increases indefinitely after exposure ceases, approximately as the square of time since first exposure lagged 10 years. These assumptions were evaluated using raw data from cohorts where exposures were principally to chrysotile (South Carolina textile workers, Hein et al., 2007; mesothelioma only data from Quebec miners and millers, Liddell et al., 1997) and crocidolite (Wittenoom Gorge, Australia miners and millers, Berry et al., 2004) and using published data from a cohort exposed to amosite (Paterson, NJ, insulation manufacturers, Seidman et al., 1986). Although the linear EPA model generally provided a good description of exposure response for lung cancer, in some cases it did so only by estimating a large background risk relative to the comparison population. Some of these relative risks seem too large to be due to differences in smoking rates and are probably due at least in part to errors in exposure estimates. There was some equivocal evidence that the relative risk decreased with increasing time since last exposure in the Wittenoom cohort, but none either in the South Carolina cohort up to 50 years from last exposure or in the New Jersey cohort up to 35 years from last exposure. The mesothelioma model provided good descriptions of the observed patterns of mortality after exposure ends, with no evidence that risk increases with long times since last exposure at rates that vary from that predicted by the model (i.e., with the square of time). In particular, the model adequately described the mortality rate in Quebec chrysotile miners and millers up through >50 years from last exposure. There was statistically significant evidence in both the Wittenoom and Quebec cohorts that the exposure intensity-response is supralinear(1) rather than linear. The best-fitting models predicted that the mortality rate varies as [intensity](0.47) for Wittenoom and as [intensity](0.19) for Quebec and, in both cases, the exponent was significantly less than 1 (p or =3:1. Moreover, PCM does not distinguish between asbestos and nonasbestos particles. One possible reason for the discrepancies between the K(L)'s and K(M)'s from different studies is that the category of structures included in PCM counts does not correspond closely to biological activity. In the accompanying article (Berman and Crump, 2008) the K(L)'s and K(M)'s and related uncertainty bounds obtained in this article are paired with fiber size distributions from the literature obtained using transmission electron microscopy (TEM). The resulting database is used to define K(L)'s and K(M)'s that depend on both the size (e.g., length and width) and mineralogical type (e.g., chrysotile or crocidolite) of an asbestos structure. An analysis is conducted to determine how well different K(L) and K(M) definitions are able to reconcile the discrepancies observed herein among values obtained from different environments.

The Database Solution to Particle-by-Particle Analysis of Mixed Mineral Dusts

Abstract This work involves the development and application of a database for the morphological, crystallographic, and chemical characterization of amphibole particles that occur as accessory minerals in the former vermiculite mine in Libby, Montana. The data in the database were collected using transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) techniques for particle-by-particle characterization of mixed mineral dust samples. In the fall of 1999, public attention was focused on the small town of Libby due to health concerns over potential amphibole asbestos exposure that occurred in the now closed vermiculite mine. The vermiculite deposit, located in the Rainy Creek Igneous Complex, about seven miles northeast of Libby, was discovered in 1913 and commercial production of vermiculite began in 1923.

Asbestos and Autoimmunity: More Bad News from Libby?

Vol. 113, No. 1 EnvironewsOpen AccessAsbestos and Autoimmunity: More Bad News from Libby?is accompanied byAssessment of Autoimmune Responses Associated with Asbestos Exposure in Libby, Montana, USA Rebecca Renner Rebecca Renner Search for more papers by this author Published:1 January 2005https://doi.org/10.1289/ehp.113-a51Cited by:1AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus seem to be the product of a complex and poorly understood interaction between environmental exposures and genetic predisposition. Autoantibodies may be markers of subclinical disease, so epidemiological studies that look for autoantibodies in populations exposed to likely environmental triggers offer one possible way to better understand this gene–environment interaction. To study whether asbestos could be such an environmental trigger, Jean Pfau and colleagues at the University of Montana in Missoula went to the nearby town of Libby, where they found evidence that asbestos exposure may indeed induce autoimmunity [EHP 113:25–30].Asbestos exposure in Libby stems from the mining of vermiculite, which is used for insulation and fireproofing. The vermiculite, mined extensively from the 1920s to 1990, was laced with toxic amphibole asbestos, and the mining operations released asbestos into the air and contaminated the mine, processing sites, and many of the buildings and properties in town. Homes also became polluted through the use of vermiculite for insulation and garden fill, according to U.S. Environmental Protection Agency investigations. Virtually the entire town was designated a Super-fund National Priorities List site in October 2002.The decades of occupational and environmental exposure to amphibole asbestos in Libby have been linked to a high incidence of asbestos-related diseases including fibrosis, pleural plaques, and cancer. Anecdotal evidence suggests there may also be a link in Libby between asbestos exposure and autoimmunity. In a 2000–2001 screening of 7,307 Libby area residents by the Agency for Toxic Substances and Disease Registry, 6.7% reported having been diagnosed with an autoimmune disease. Pfau and colleagues note that figure typically should be less than 1%.In the current study, the researchers sampled the blood of 50 middle-aged men and women from Libby and 50 matched controls from Missoula, where there is no known asbestos exposure. The samples were analyzed for antinuclear antibodies (ANAs) using a commercially available indirect immunofluorescence test. ANAs are a class of autoantibody often found in the blood of people whose immune systems may be predisposed to cause inflammation against their own body tissues. The researchers also looked for correlations between length of asbestos exposure, presence of asbestos-related disease, and ANA levels among the Libby subjects.They found that ANAs occurred 28.6% more frequently in the Libby samples than in those from Missoula. This finding is consistent with the results of a limited number of other studies of populations exposed to asbestos. In addition, individuals who had been exposed to asbestos for more than five years tended to have higher concentrations of ANAs than those with less exposure. Of the people from Libby, 12 had no lung abnormalities, but the rest had asbestos-related lung problems; those with more severe lung problems also had higher concentrations of autoantibodies.Based on the correlation between asbestos-related disease and ANA levels, the results suggest that asbestos is an agent of systemic autoimmunity and that autoimmune responses may play a role in the progression of asbestos-related diseases, according to the authors. Pfau and colleagues intend to continue their studies of actual autoimmune diseases among the Libby population.Libby, Libby, Libby. The saga continues for the residents of Libby, Montana, as new research suggests that amphibole asbestos exposure may induce autoimmunity.FiguresReferencesRelatedDetailsCited by Murray A, Kisin E, Tkach A, Yanamala N, Mercer R, Young S, Fadeel B, Kagan V and Shvedova A (2012) Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos, Particle and Fibre Toxicology, 10.1186/1743-8977-9-10, 9:1, (10), . Related articlesAssessment of Autoimmune Responses Associated with Asbestos Exposure in Libby, Montana, USA30 September 2004Environmental Health Perspectives Vol. 113, No. 1 January 2005Metrics About Article Metrics Publication History Originally published1 January 2005Published in print1 January 2005 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. 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Dielectric changes in membrane properties and cell interiors of human mesothelial cells in vitro after crocidolite asbestos exposure.

Asbestos induces cytogenetic and genotoxic effects in cultured cell lines in vitro. For further investigations of the fiber-induced cellular changes, electrorotation (ROT) measurements can be used to determine early changes of surface properties and dielectric cellular changes. In the present study, human mesothelial cells (HMC) were exposed to nontoxic concentrations of crocidolite asbestos (1 microg/cm(2)) for 12, 24, 30, 50, and 72 hr, and were investigated for changes in dielectric properties, morphologic and biochemical changes using ROT measurements, electron microscopy, and flow cytometry, respectively. The results of ROT measurements revealed slightly increased internal conductivity and decreased membrane conductance of HMC during the first 12 hr of exposure to crocidolite. This may be due to functional changes of ion channels of the cellular membrane. However, after exposures of >= 30 hr, reduced internal conductivity and increased membrane conductance of HMC occurred. These effects may be caused by permeabilization of the cell membrane and the leakage of ions into the surrounding medium. The membrane capacitance of HMC is always decreased during exposure of cells to crocidolite fibers. This decreased membrane capacitance may result from the observed reduction in the number of microvilli and from the shrinkage of cells as observed by electron microscopy and flow cytometry. Changes in composition of the plasma membrane were also observed after the labeling of phosphatidylserines (PS) on the cell surface. These observed changes can be related to apoptotic events. Whereas during the first 50 hr of exposure only a small number of HMC with increased exposure of PS on the cell surface was detected by flow cytometry, the dielectric properties of HMC showed marked changes during this time. Our results show that surface property changes of the cellular membrane of HMC as well as interior dielectric changes occur after the exposure of cells to crocidolite fibers. The observed changes are discussed in terms of complex combined cellular effects after amphibole asbestos exposure.