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PubMed1991

Relationship between cumulative occupational exposure to asbestos fibres and respiratory symptoms.

A survey of chronic respiratory symptoms was undertaken in 1127 asbestos workers engaged in asbestos mining, asbestos cement production, production of friction materials or in the manufacture of asbestos textile. A control group of 593 persons was also surveyed. The exposure of asbestos workers was analysed by evaluating separately the cumulative exposure to total airborne particles and to airborne asbestos fibres. The prevalences of all the respiratory symptoms (chronic cough, chronic phlegm, chronic bronchitis, dyspnoea grade 3+) were significantly higher in asbestos workers compared to controls in both nonsmokers and smokers (p less than 0.01). The prevalences of all the respiratory parameters in asbestos workers increased with both the length of employment and cumulative exposure to total airborne particles. Prevalences of chronic cough, chronic phlegm and chronic bronchitis did not show an increase with cumulative exposure to airborne asbestos fibres expressed as fibres/cc years. It is concluded that the development of chronic cough, chronic phlegm and chronic bronchitis in asbestos workers is likely to be an unspecific effect of the exposure to the difficulty soluble airborne particles rather than a specific effect of the exposure to airborne asbestos fibres.

Adolescent↗

PubMed1990

Serum promotes asbestos-induced injury to human pulmonary epithelial cells.

Asbestos exposure causes chronic interstitial pulmonary fibrosis. Injury to human pulmonary epithelial cells (HPEC) is speculated to precede the fibrotic response. We investigated whether asbestos, either alone or in conjunction with serum, injured cultured HPEC as assessed in a standard chromium 51 release assay. Amosite asbestos in serum-free media induced modest HPEC injury (9.4% +/- 3.3% Cr release), which was significantly enhanced (2.7-fold) in the presence of serum (25.5% +/- 4% Cr release). HPEC cytotoxicity was both asbestos and serum dose-dependent. Additionally, we demonstrated that, compared with HPEC injury induced by asbestos plus serum, (1) heat-decomplemented serum or serum fractions of a wide range of molecular weights were equipotent to fresh serum, (2) catalase, superoxide dismutase, or dimethylthiourea was not protective, (3) 3-aminobenzamide, which prevents oxidant-induced adenosine triphosphate depletion by inhibiting poly-adenosine diphosphate-ribose polymerase, afforded significant protection (32% decrease in HPEC injury), and (4) deferoxamine-treated asbestos was significantly less toxic to HPEC compared with untreated asbestos, causing a 57% decrease in HPEC cytotoxicity. Electron microscopic studies revealed that, compared with buffer, serum increased the amount of amosite asbestos along the surface and inside HPEC. Thus, amosite asbestos is cytotoxic to cultured HPEC and serum promotes this injurious effect by augmenting the interaction of asbestos with HPEC. These data suggest that this effect may occur by increasing intracellular oxidant stress mediated in part by the iron in asbestos.

Asbestos↗

PubMed1985

Inhaled asbestos activates a complement-dependent chemoattractant for macrophages.

Pulmonary macrophages migrate to the sites where inhaled chrysotile asbestos fibers initially are deposited (i.e., surfaces of alveolar duct bifurcations). These macrophages have been shown to form a major component of an early asbestos-induced interstitial lesion in rats. In this report, we describe a potential mechanism by which macrophages are attached to these sites of fiber deposition. Chrysotile asbestos fibers used in vitro activate complement proteins in peripheral blood serum and in lavaged cell-free lung proteins. After brief inhalation of chrysotile asbestos, fluids lavaged from the lungs of exposed rats contain substantial chemotactic activity for macrophages compared to fluids from sham-exposed animals (p less than 0.01). We hypothesize that this chemotactic activity is derived from complement activated by inhaled asbestos on alveolar surfaces. This contention is supported by the following observations. Production of chemotactic activity by asbestos in vitro in serum or in lavaged lung fluids was blocked by complement inhibitors. Fractionation, by molecular sieve chromatography, of serum proteins and concentrated proteins lavaged from the lungs of asbestos-exposed rats showed that chemotactic activity was detected in the 14,000- to 18,000-dalton range. This fractionation profile is similar to C5a, the chemotactic product of complement activation. Rats treated with cobra venom factor to deplete circulating complement as well as complement-deficient mice demonstrated significantly depressed macrophage accumulation at sites of asbestos deposition. Pulmonary macrophages are the cells that form the initial inflammatory response to asbestos inhalation. Our findings support the hypothesis that asbestos fibers, and possibly other inhaled particulates, activate complement-derived chemotactic activity on alveolar surfaces. Consequently, macrophages are attracted to the alveolar duct bifurcations where inhaled asbestos fibers are deposited, and this is where the initial lesion of asbestosis is manifested.

Animals↗

PubMed1982

Correlation of asbestos bodies and fibers in lungs of subjects with and without asbestosis.

We compared the numbers of asbestos bodies in 2 histologic sections of lung from 25 subjects showing a wide range of total asbestos burden with the numbers of asbestos bodies and fibers (analyzed by electron diffraction and x-ray spectroscopy) extracted from the lung. We also compared the numbers of extracted asbestos bodies with the numbers of fibers in 24 other subjects. Histologic and extracted asbestos bodies were correlated best with total asbestos fibers and with amosite and crocidolite fibers, and not at all with chrysotile fibers. Nevertheless, the total fiber count could not be reliably estimated from the count of either histologic or extracted bodies. Although asbestos bodies appeared to be fairly uniformly distributed in these lungs, detection of early fibrosis or asbestosis required careful examination of all portions of the parenchyma. When we defined asbestos histologically as clusters of 3 or more asbestos bodies adjacent to areas of fibrosis, we found that subjects with asbestosis had more than 240,000 asbestos fibers/g of wet lung. The nature of the disease in lungs showing fibrosis and more than 240,000 fibers/g, but only isolated asbestos bodies, is uncertain.

Adult↗

PubMed1983

[Malignant diseases of the respiratory organs caused by asbestos exposure in municipal environment].

Exposure of population to asbestos comes from several origins. It is proved by measuring of asbestos emission and by discoveries of asbestos emission and by discoveries of asbestos fibres in lungs of adults. Asbestos induced maladies are not only founded after professional exposition, but also sometimes after domestic asbestos contacts or in neighbours of asbestos processing firms (generally upon a long time past influence of asbestos holding emissions). There is no evidence for an increase of the frequency of asbestos induced cancer in the inhabitants of large towns and industrial centres of GDR, till now. Morbific effects of asbestos must be expected in special risk groups. All efforts are necessary to reduce asbestos in known dust touched spheres.

Air Pollution↗

PubMed1981

[Risk factor asbestos (author's transl)].

In the G.D.R. asbestos is used at a large industrial scale. The material is of interest for oncologists and industrial hygienists due to its fibrogenic and cancerogenic potencies. Both carcinomas of the respiratory organs and the rare malignant mesotheliomas are accepted as occupational diseases due to asbestos. In a retrospective study 915 cases of malignant mesotheliomas covered by the National Cancer Registry over a period of 6 years--all histologically established--were analysed. 36.7% originated from occupational handling of asbestos, 0.8% by non-occupational asbestos contacts. In another 9.1% of the cases asbestos may have been the underlying cause. 33.7% have had no asbestos contact; for 19.7% the data available were insufficient. Among the asbestos-containing materials used packing and insulating materials were prevailing in 47.7%, asbestos-containing talc in 19.6%. In 6.9% of the cases mesothelioma affection was due to wearing fire protective clothing. Different duration of exposure and especially long latency periods demonstrates difficulties interpreting the results concerning the relation between working conditions and illness. Primary (technical) prevention by reduction of asbestos dust emission, limited use of asbestos and lifelong monitoring of asbestos workers are necessary to reduce the tumour risk.

Adolescent↗

PubMed1995

Asbestos contamination in paraffin tissue blocks.

Electron microscopic analyses of tissue samples embedded in paraffin are routinely performed as a means of validating (establishing) the asbestos exposure of persons diagnosed with mesothelioma, a rare form of cancer often identified as being caused by exposure to asbestos. During analysis of tissue samples claimed to contain asbestos, we observed asbestos contamination in the paraffin of the tissue block. To investigate the extent to which such contamination is prevalent in tissue block samples, we obtained and analyzed samples of paraffin blocks from hospitals in six major cities and found them to contain measurable concentrations of asbestos. Whether this asbestos contamination originated in the virgin wax or was a result of processing has not been established. This result, which has not been previously reported, raises significant concerns about the validity of analyses for asbestos in tissue embedded in paraffin. In particular, diagnoses in which the presence of asbestos in tissue samples is taken as being indicative of past asbestos exposure, especially for those cases in which no known exposure has occurred, and studies purporting to show migration of asbestos to other organs in the body following inhalation or ingestion of asbestos require critical reevaluation. The need for reevaluation is particularly acute if appropriate control blanks were not evaluated as part of the studies.

Asbestos↗

PubMed1983

The effects of chrysotile and crocidolite asbestos on the lower respiratory tract: analysis of bronchoalveolar lavage constituents.

This study was designed to evaluate the effects of amphibole and serpentine asbestos inhalation on the constituents of the lower respiratory tract. Bronchoalveolar lavage (BAL) analyses were performed on three groups of rats: one group was exposed to chrysotile (serpentine) asbestos, another group was exposed to crocidolite amphibole asbestos, while a third group was sham-exposed. Intermittent inhalational exposures lasted three months. The total BAL cell yields and the macrophage content of BAL cells were significantly lower after asbestos exposure, especially in the chrysotile-exposed group. These effects persisted for as long as 1 year after the cessation of exposure. Multinucleated macrophages were seen in BAL cells from both asbestos-exposed groups. Striking ultrastructural alterations of macrophage morphology were noted in BAL cells from both groups of asbestos-exposed rats. Chrysotile fibers were not seen in any BAL cells from chrysotile-exposed animals. However, 15 months after terminating the exposure regimen, a sizeable proportion of BAL macrophages from crocidolite-exposed rats contained phagocytosed asbestos fibers. Significantly higher beta-glucuronidase and lactate dehydrogenase activity was found in BAL fluids from both asbestos-exposed groups and was detected 17-18 months after exposure had ceased. These observations have served as useful correlates of asbestos-mediated injury to the lower respiratory tract. They have also provided evidence of continual pathological sequelae occurring long after withdrawal from asbestos exposure.

Animals↗

PubMedDate not supplied

Asbestos burden in cases of mesothelioma from individuals from various regions of the United States.

Mesothelioma is a rare tumor that is considered an asbestos marker disease. It occurs in individuals following a longer latency period from first exposure than other asbestos-related diseases. The tumor also occurs in individuals with a wide range of exposures, including individuals with lower level or secondary exposures. In the present study lung tissue from 54 individuals with a pathological diagnosis of mesothelioma was evaluated for ferruginous body and uncoated asbestos fiber content. The data were compared with an earlier study of mesothelioma cases from the northwestern United States. Tissue was prepared via a digestion procedure, with the collected digestate reviewed by light microscopy for quantification of asbestos bodies and analytical transmission electron microscopy for determination of uncoated fiber burden. Twenty-seven cases in the present study had over 1000 ferruginous bodies per gram of dry tissue. The data suggest that amosite provides a more likely stimulus for ferruginous coating than the other forms of asbestos. All individuals were found to have asbestos fibers in their lung tissue. Amosite was the most commonly found fiber, with anthophyllite being the second most commonly found type of asbestos. The finding of tremolite in the tissue most often was associated with the finding of anthophyllite. A limited number of asbestos fibers of each type would have been seen in the light microscope, with the least detected being chrysotile. The majority of all fiber types were found as short fibers (< 8 mum), although some longer fibers were represented in each type of asbestos. The majority of the individuals were found to have mixed types of asbestos in their lungs.

Adult↗

PubMed1993

Cytotoxic and cytogenetic effects of asbestos on human bronchial epithelial cells in culture.

Asbestos and other mineral fibers elicit responses in several rodent cell transformation systems. The mechanism of this transformation has been hypothesized to involve specific chromosome alterations, especially changes in chromosome number. However, the cytogenetic effects of asbestos fibers in cultured human respiratory epithelium have not been well characterized. The present study examined the effects of chrysotile and crocidolite asbestos fibers on cultures of human bronchial epithelial (HBE) cells growing in serum-free medium. HBE cells were continuously treated with chrysotile (0-4 micrograms/cm2) or crocidolite (0-300 micrograms/cm2) asbestos and examined after 24, 48, 72 or 96 h for cytotoxic and cytogenetic effects. Both asbestos fiber types induced a concentration-dependent inhibition of cell proliferation and colony-forming efficiency; however, in these assays chrysotile was 100-300 times more toxic than crocidolite. Concentrations of asbestos that inhibited growth had little effect upon trypan blue exclusion or intracellular esterase activity, suggesting that the majority of asbestos-exposed cells were still viable. A 2.7-fold increase in binuclei and a 1.6-fold increase in micronuclei were observed 72 h after treatment with 4 micrograms/cm2 chrysotile. A 1.9-fold increase in binuclei was observed 72 h after treatment with 300 micrograms/cm2 crocidolite, but crocidolite did not increase the incidence of micronuclei. Chrysotile asbestos failed to induce significant numerical chromosome changes in HBE cells and increased structural aberrations only at the 24 h time point. These findings contrast with the relatively high incidences of asbestos-induced chromosome changes previously observed in some rodent cell cultures and suggest the existence of species-specific or cell-type-specific differences in either chromosome stability or mechanism(s) of asbestos-induced toxicity.

Asbestos↗

PubMed1990

NTP Lifetime Carcinogenesis Studies of Chrysotile Asbestos (CAS No. 12001-29-5) in Syrian Golden Hamsters (Feed Studies).

NTP Carcinogenesis studies of short range (SR), intermediate range (IR), or intermediate range chrysotile asbestos in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted with male and female Syrian golden hamsters. Both forms of chrysotile asbestos were administered at the concentration of 1% in pelleted diet for the entire lifetime of the hamsters starting with mothers of the test animals. Group sizes varied from 125 to 253. Starting at 6 weeks of age, male and female hamsters in the intermediate range chrysotile/DMH study were given oral doses of DMH (4 mg/kg) every other week for a total of 5 doses. There was no adverse effect on body weight gain or survival by either form of asbestos or by asbestos in combination with DMH. A significant increase (P< 0.05) in adrenal cortical adenomas was observed in male hamsters exposed to SR and IR chrysotile asbestos and in females treated with IR chrysotile asbestos when compared to the pooled control groups (males: pooled controls, 25/466, 5%; SR chrysotile, 26/299, 11%; IR chrysotile, 24/244, 10%; females: pooled controls, 15/468, 3%; IR chrysotile, 18/234, 8%). However, statistical significance was lost when these dosed groups were compared with concurrent control groups (males: SR control, 7/115, 6%; IR control, 7/115, 6%; females: SR control, 4/112, 4%; IR control, 6/118, 5%). The results of the combination study (IR chrysotile plus DMH) did not yield a significant increase in tumors above the background level observed in the DMH group alone or in the untreated control group. The DMH failed to yield a background level of intestinal tumors high enough to provide a valid test of the cocarcinogenic potential of chrysotile asbestos. For this reason, the cocarcinogenic potential of orally administered asbestos should be considered untested. Under the conditions of these studies, neither short range chrysotile nor intermediate range chrysotile asbestos was carcinogenic when ingested at 1% levels in the diet by male and female Syrian golden hamsters. While there were increases in the rates of adrenal cortical adenomas in male and female hamsters exposed to intermediate range chrysotile asbestos compared to the pooled groups, these incidence rates were not different when compared with the concurrent control groups. Additionally, the biologic importance of adrenal tumors in the absence of target organ (gastrointestinal tract) neoplasia is questionable. The coNTP Carcinogenesis studies using IR chrysotile asbestos and 1,2-dimethylhydrazine dihydrochloride were considered inadequate because there was no increase in intestinal neoplasia in the DMH group. Levels of Evidence of Carcinogenicity: Intermediate Range: Male Hamsters: Negative Female Hamsters: Negative Intermediate Range + dimethyl hydrazine: Male Hamsters: Inadequate Female Hamsters: Inadequate Short Range: Male Hamsters: Negative Female Hamsters: Negative.

Journal Article↗

PubMed1996

Asbestos exposure and ovarian fiber burden.

Epidemiologic studies suggest increased risk of epithelial ovarian cancer in female asbestos workers and increased risk of malignancy in general in household contacts of asbestos workers. Ovaries were studied from 13 women with household contact with men with documented asbestos exposure and from 17 women undergoing incidental oophorectomy. Ovarian tissue was examined by analytic electron microscopy. Significant asbestos fiber burdens were detected in 9 out of 13 women with household asbestos exposure (69.2%), and in 6 out of 17 women who gave no exposure history (35%). Three exposed women had asbestos counts over 1 million fibers per gram wet weight (23%), but only 1/17 women without an exposure history had a count that high (6%). Although asbestos has been documented as a contaminant of some older cosmetic talc preparations, the chrysotile and crocidolite types of asbestos we detected are more indicative of background and/or occupational exposure. This study demonstrates that asbestos can reach the ovary. Although the number of subjects is small, asbestos appears to be present in ovarian tissue more frequently and in higher amounts in women with a documentable exposure history.

Asbestos↗

PubMed2000

Association between 8-hydroxy-2'-deoxyguanosine levels in DNA of workers highly exposed to asbestos and their clinical data, occupational and non-occupational confounding factors, and cancer.

In the preceding paper [B. Marczynski, P. Rozynek, T. Kraus, St. Schlösser, H.J. Raithel, X. Baur, Levels of 8-hydroxy-2'-deoxyguanosine in DNA of white blood cells from workers highly exposed to asbestos in Germany, Mutat. Res. (2000) submitted] we described significant increases (p<0.001) in the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adducts in the DNA of white blood cells (WBC) of workers highly exposed to asbestos fibers at the workplace relative to those found in the control group in all three study years (period between 1994 and 1997). The results show that the oxidative DNA damage in exposed individuals is between 1.7 times and twice that found in control samples for all 3 years of the study (p<0.001). The aim of this study was to examine the association between the 8-OHdG levels in WBC DNA of workers highly exposed to asbestos fibers at the workplace and clinical data, occupational and non-occupational confounding factors, and cancer. There is no obvious correlation between the steady-state levels of 8-OHdG in the circulating WBC DNA of asbestos workers and possible confounding factors, such as the presence of benign asbestos-associated diseases, the duration of asbestos exposure, the latency period, the fixed cumulative fibrous dust dose ("fiber years"), age, smoking status, acute febrile infections, medicines, aspirin, calcium (Ca(2+)), magnesium (Mg(2+)), and the hormone and vitamin intake. This indicates that previous inhalation of asbestos fibers is the major factor responsible for the difference observed in oxidative DNA damage between asbestos workers and controls. For patients suffering from respiratory cancer, cancer of the gastrointestinal tract, mouth/pharynx/larynx, and urogenital tract the mean DNA-adduct level was significantly higher (p<0.01) than that found in controls, but not significantly higher (p>0.05) than that for asbestos-exposed patients without tumours. The formation of 8-OHdG adduct levels in WBC DNA of patients with hematopoietic cancer, chondrosarcomas and multiform glioblastomas was not significantly higher than that found in the control group (p>0.05). Our results support the hypothesis that oxidative DNA damage in man caused by asbestos fibers plays a role in the formation of malignant tumours.

8-Hydroxy-2'-Deoxyguanosine↗

PubMedDate not supplied

Risk assessment of lung cancer and mesothelioma in people living near asbestos-related factories in Taiwan.

Estimates from environmental risk assessments are criticized by professionals who indicate that inaccuracies occur in exposure assessment, model selection, and determination of the population at risk. In the current study, we tackled the aforementioned issues and estimated the risks of lung cancer and mesothelioma caused by airborne asbestos among individuals who lived near asbestos factories in Taiwan. We conducted 8-h full-period samplings upwind and downwind from each factory, and we used transmission-electronic microscopy (10,000x) and phase-contrast microscopy to determine asbestos concentrations in and around each factory. We estimated the numbers of residents who lived in concentric circles of 200-m, 400-m, and 600-m diameters around each factory. A dose-response model for asbestos-induced lung cancer was adopted from a summary of seven epidemiological studies. The asbestos-mesothelioma models were patterned after the first-exposure-effect models developed by Peto and Finkelstein. The data obtained from phase-contrast microscopy significantly overestimated the risk, compared with transmission-electronic microscopy. The estimates we calculated from adopting the arithmetic mean were approximately 2-fold higher than those we calculated with the geometric mean. There were relatively low concentrations of asbestos in the study areas, thus causing an absence of a significant difference in risk estimates between different models for mesothelioma. Among the more than 20,000 residents who lived near 41 asbestos factories in Taiwan, we found that the numbers of expected excess deaths from lung cancer and mesothelioma were 5 and less than 1, respectively. We concluded that in future risk assessments for ambient asbestos exposure, investigators should adopt transmission-electronic microscopy and the geometric mean estimate. Moreover, Taiwan should enhance asbestos-control programs to assure the safety of residents who live near asbestos factories.

Adult↗

PubMed1987

Cigarette smoke makes airway and early parenchymal asbestos-induced lung disease worse in the guinea pig.

In order to assess the effects of cigarette smoke and asbestos exposure, we divided guinea pigs into 4 groups: smoking or nonsmoking, and asbestos-exposed or not asbestos-exposed groups. Asbestos-exposed animals were given a single intratracheal instillation of 5 mg UICC amosite, a dose and method of administration that we have previously shown produces morphologic changes in the small airways as well as minimal interstitial fibrosis. Animals were smoked 5 days per week for 6 months. By itself, smoking did not affect lung collagen content, small airways wall thickness, or the volume fraction of tissue surrounding airways, but it did cause a significant increase in alveolar mean linear intercept (Lm). Asbestos alone increased collagen content, airway wall thickness, and tissue volume fraction surrounding airways, the latter measure used to assess interstitial fibrosis. An unexpected finding was that asbestos also increased Lm. The two agents administered together caused more severe changes of all types than were produced by either agent alone, and the interaction between the 2 was generally synergistic. Smoke-exposed animals retained 3 times the asbestos fiber burden of those not smoke-exposed; the increase in retention was greater for short than for long fibers. We conclude that cigarette smoke can potentiate the fibrosis induced by asbestos, possibly because of increased fiber retention. As well, in this model, asbestos or asbestos plus cigarette smoke produces increases in alveolar size.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Asbestos fibers and interferon-gamma up-regulate nitric oxide production in rat alveolar macrophages.

The present study was undertaken to determine whether asbestos exposure induces the formation of nitric oxide (NO.) radical by rat alveolar macrophages (AM). For this purpose, AM from Sprague-Dawley rats were cultured for 48 h in the presence or absence of either chrysotile (serpentine) or crocidolite (amphibole) asbestos fibers. The effects of asbestos fibers were compared with those of nonfibrogenic carbonyl iron particles. Nitrite (NO2-), the stable oxidation product of NO. in macrophage conditioned medium, was assayed by the Griess reaction. Production of NO2- by AM was significantly increased by both chrysotile (P < 0.01) and crocidolite (P < 0.05) asbestos fibers (10 micrograms/ml). Since interferon-gamma (IFN-gamma) is known to induce NO. synthase within macrophages, and since elevated levels of intrapulmonary IFN-gamma have been noted in asbestos workers, the combined effects of asbestos and IFN-gamma also were studied in the context of NO. formation. Addition of IFN-gamma (250 to 500 IU/ml) synergistically enhanced the formation of NO2- induced by chrysotile and crocidolite. Notably, carbonyl iron had no significant effect on NO. production by AM. NO2- production was significantly attenuated by the NO. synthase inhibitor, NG-monomethyl-L-arginine (0.5 to 1 mg/ml). By contrast, superoxide dismutase (150 U/ml) significantly enhanced asbestos-induced NO2- production by AM (P < 0.001). Since superoxide anion can interact with NO. to generate the toxic hydroxyl radical, and since superoxide dismutase is known to protect against asbestos-induced injury, the induction of NO. radical by asbestos fibers may represent a novel form of asbestos-related injury.

Amino Acid Oxidoreductases↗

PubMed1999

Asbestos upregulates expression of the urokinase-type plasminogen activator receptor on mesothelial cells.

Inhalation of asbestos is associated with pathologic changes in the pleural space, including pleural thickening, pleural plaques, and mesothelioma. These processes are characterized by altered local proteolysis, cellular proliferation, and cell migration, suggesting that the urokinase-type plasminogen activator receptor (uPAR) could be involved in the pathogenesis of asbestos-induced pleural disease. We hypothesized that mesothelial cell uPAR expression is induced by exposure to asbestos. To test this hypothesis, we used complementary techniques in rabbit and human mesothelial cells to determine whether uPAR expression is altered by exposure to asbestos. uPAR expression was induced by chrysotile and crocidolite asbestos, but not by wollastonite, as indicated by binding of radiolabeled urokinase-type plasminogen activator (uPA) to rabbit or human mesothelial cells. uPA was not induced by fiber exposure. Exposure to exogenous uPA increased uPA activity of cells exposed to wollastonite but not asbestos-treated MeT5A cells. uPAR expression increased further when asbestos was preincubated with vitronectin (VN) or serum. Increases in uPAR expression were confirmed by binding of uPA to uPAR in cell membrane preparations and immunofluorescent staining of uPAR at the cell surface, and were associated with increases in steady-state uPAR messenger RNA. Mesothelial cell uPAR expression was also induced by media from monocytes cultured with asbestos incubated with VN and serum. By antibody neutralization, the latter effect appeared to be in part mediated by transforming growth factor-beta. We found that asbestos increases uPAR at the surface of rabbit and human mesothelial cells, suggesting that altered expression of this receptor could be involved in asbestos-induced remodeling of the pleural mesothelium.

Animals↗

PubMed1983

Thermal modification of chrysotile asbestos: evidence for decreased cytotoxicity.

Many asbestiform minerals exhibit temperature-dependent thermoluminescence. Since thermoluminescence involves electronic transitions within crystalline materials, the effect of temperature on asbestos cytotoxicity was evaluated. Heat pretreatment of Canadian chrysotile asbestos reduces its cytotoxicity towards cultured human fibroblasts and bovine alveolar macrophages. When monitored 44 hr after the addition of either 200 degrees C or 400 degrees C heat-pretreated asbestos, alveolar macrophage viability was approximately 40% higher than comparable amounts of unheated asbestos. Similarly, asbestos toxicity, expressed as fibroblast growth inhibition, was inversely related to the asbestos pretreatment temperature in the following manner, 70 degrees C greater than 200 degrees C greater than 400 degrees C = unexposed fibroblast controls. Pretreatment of chrysotile asbestos to 400 degrees C reduced its adsorptive capacity for bovine serum albumin by 25%. Furthermore, asbestos heated to 200 degrees C followed by irradiation with 4 MeV X-rays (4500 rads) resulted in reactivation of asbestos cytotoxicity. Scanning electron microscopy indicated that the ratios of free to fiber-associated alveolar macrophages and the fiber fragment size distributions were unaffected by either heat pretreatment or X-ray irradiation. These observations strongly suggest that the surface charge characteristics and electronic state of asbestos fibers may be responsible for its biological activity.

Adsorption↗