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[Concentration of asbestos fibers in urothelial tumors and in the neoplasm-free bladder wall].

The aim of our study was to search the eventual presence of asbestos fibers in the neoplastic tissue of 13 cases of bladder carcinoma and in the normal vesical tissue of 12 control cases without neoplasia and operated upon for other urologic pathologies. To all patients a standardised questionnaire has been administered in order to ascertain the entity of the eventual exposition to asbestos. The organic component of the tissues has been oxidated at low temperature in atomic oxygen plasma and the residual inorganic component has been analysed by transmission electronic microscopy and energy dispersion spectrometry. We have found asbestos fibers only in two over the 25 examined samples; in both cases they belonged to patients affected by the neoplasia and in one of them also by pulmonary asbestos. The procedures that we used in this study, in respect to our other experiences, allowed us to reduce the risk of contamination of the tissues by asbestos, as it is shown by the lower number of cases with positive finding of fibers and by lower concentration of fibers in the positive cases.

Adult↗

[Diffuse malignant mesothelioma associated with asbestos pleurisy].

Asbestos pleurisy is relatively uncommon among patients who present with pleural fluid. Association of diffuse malignant mesothelioma with asbestos pleurisy has not been reported in Japan, although 10 cases have been reported in the world literature. We encountered a 51-year-old man in whom diffuse malignant mesothelioma developed during a 5-year course of asbestos pleurisy. Mesothelial cells in patients with asbestos pleurisy are likely to be exposed to asbestos for a long time, which may increase the risk that mesothelioma will develop.

Asbestos↗

Latency periods in asbestos-related mesothelioma of the pleura.

Latency periods (time intervals elapsing between first exposure to asbestos and death) were examined in 421 cases of malignant pleural mesothelioma, diagnosed in the Trieste-Monfalcone area, Italy. Occupational data were collected from the patients or from their relatives by personal or telephone interviews. Routine lung sections were examined for asbestos bodies in 370 cases. Latency periods, calculated in 312 cases, ranged from 14 to 72 years (mean 48.7, median 51). Latency periods differed significantly from one occupational group to another. Mean latency periods were 29.6 among insulators, 35.4 among dock workers, 43.7 in a heterogeneous group defined as various, 46.4 in non-shipbuilding industry workers, 49.4 in shipyard workers, 51.7 among women with a history of domestic exposure to asbestos, and 56.2 in people employed in maritime trades. The ANOVA test indicated a correlation between latency periods and occupational groups. Latency periods in people with asbestos bodies visible in routine lung sections did not differ from those seen in cases with no evidence of asbestos bodies. These data suggest that intensity of exposure is a relevant, but not the only, factor in determining the duration of latency periods.

Adult↗

[Evaluation of health hazards of asbestos containing wastes in the mining industry and prospects of their utilization].

The study covered asbestos-containing waste at a major mining enrichment enterprise--"Uralasbest" JSC. A set of methods were used to associate natural human compensatory mechanisms with experimental models simplifying possible routes of asbestos influence on humans and proved no toxic features of the dust studied. The results help to manage removal and storage of asbestos-containing waste, to use it for production of various building materials. However, variable asbestos (free and fixed) content of the waste and admixtures of chromium, nickel and other elements in it prevent from utilisation of asbestos waste at other enterprises and necessitate further hygienic evaluation.

Asbestos↗

Determination of tissue polypeptide antigens (TPA) and carcinoembryonic antigen (CEA) in serum: its value in the preliminary cancer risk assessment in asbestos exposed workers.

Seeking the changes at the cellular level or at the level of cellular metabolism products, present in the biological fluids, in order to detect early stages of the carcinogenic process is an essential step in preventing cancer development among asbestos exposed workers. Carcinogenic biomarkers such as tissue polypeptide antigens (TPA) and carcinoembryonic antigen (CEA) were found very useful in this attempt. The objective of this work was to identify individuals at critical cancer risk in the population of workers exposed to asbestos and to evaluate the value of TPA and CEA determinations for this particular purpose. The study was carried out in the group of workers exposed to asbestos (n = 274). Age, exposure duration, smoking habits and the kind of job performed, were considered in the analysis of the results. To sum up, it should be concluded that in 22 persons exposed to asbestos TPA values exceeded the cut off concentrations, established on the basis of the studies performed in the control group, and CEA value accounted for 10 ng/lm. Statistically significant differences in the percentage of TPA increased values between two groups under study were indicated. Such a relationship did not apply to CEA. In the exposed group, an evident effect of the age and exposure duration on the number of persons with TPA concentrations above the cut off, was also revealed. These changes show a growing tendency and statistical significance for TPA only. Smoking had a great impact on the occurrence of TPA increased concentrations. Three kinds of jobs were considered: operation of the production line, white collar workers and miscellaneous'. The significant differences in TPA concentrations between the operators and miscellaneous, and between white collar workers and miscellaneous were found. Therefore, it may be concluded that a similar percentage of TPA increased values was observed in the group of operators and white collar workers. The study allowed to identify, among those exposed to asbestos, 22 persons who should be covered with target medical care. It also indicated that TPA determination was more useful than that of CEA in this kind of investigations.

Adult↗

[Pulmonary CO diffusion and radiological findings in subjects formerly exposed to asbestos cement].

A cross-sectional study on 117 male former asbestos-cement workers was performed. The aims of the study were: evaluation of the prevalence of respiratory symptoms, measurement of pulmonary volumes, flows and DI(co) values, detection of asbestos-related diseases, and data collection for a medical follow-up of the participants. Medical examination included ECSC questionnaire, spirometry, DI(co) measurement and chest x-ray. Time since first exposure (latency) and duration of employment were used as exposure indices: participants were subdivided into three exposure groups, respectively for latency and duration of employment. For statistical analysis, multiple linear regression and logistic regression methods were applied; significance level was p < 0.05. In 28 participants abnormal DI(co) values (< 80% of predicted) were measured, 9 subjects (8%) had radiological asbestos-related abnormalities. Lower values of DI(co), after correcting for smoking, were observed in the third latency group of subjects; an increased risk of radiological asbestos-related abnormalities was observed in relation to the duration of employment and latency. This study confirmed DI(co) as an indicator of (asbestos-related) pulmonary interstitial disease.

Asbestos↗

A quantitative study of environmental asbestos exposure in Honolulu.

The increased use of asbestos in various industries in past decades has led to increases in environmental asbestos pollution. Incidental exposure to asbestos is inevitable, and has generated public concern. We performed the following study aimed at determining the level of environmental asbestos exposure in Honolulu, and our results indicate that the levels of environmental asbestos in Honolulu are the lowest in the nation.

Adult↗

[Non-malignant asbestos-related diseases].

Non malignant asbestos diseases are dominated numerically by pleural plaques. This form of circumscribed fibrosis of the parietal pleural is generally asymptomatic and its potential for evolution is weak. More rarely diffuse pleural fibrosis results from disease of the visceral pleura with a secondary fusion of the two pleural layers. Usually it follows a pleural effusion which resolves spontaneously. Its functional effects are sometimes important. The generalised practice of computerized tomographic scanning as a work up for asbestos related disease has revealed the frequent association of this diffuse pleural fibrosis with a particular form of peripheral pulmonary collapse called round atelectasis. Asbestosis or pulmonary fibrosis induced by the inhalation of asbestos has become rarer due to the improvement in working conditions in the asbestos industry. It develops following heavy exposure. The frequency of bronchopulmonary cancer is increased when asbestosis exists although it is not currently possible to say if the two disorders are independent and each is only conditioned by exposure to asbestos or if the two diseases are inextricably linked by the same physiopathological process.

Asbestos↗

Secular trends in prevalence and concentration of pulmonary asbestos bodies--1940 to 1972. A necropsy study.

This study was designed to inquire into changes in the prevalence and concentration of asbestos bodies in the lungs of the necropsy population in Sinai Hospital of Baltimore during a 33-year period, 1940 to 1972. A tissue digestion technique was used to extract and quantitate asbestos bodies not only in fresh samples of pulmonary tissue but also in older fixed and blocked samples. A significant increase in the proportion of lungs containing asbestos bodies was found in the later years, as well as an increase in the concentration of asbestos bodies in lungs of the older age groups. Currently, 91.1%of this necropsy population in Baltimore harbor asbestos bodies in their lungs. The biologic importance of this increase is uncertain and speculative.

Adolescent↗

[Asbestos exposure and pleuropulmonary cancer].

Pleuropulmonary cancers are recognized asbestos-related diseases. Mesothelioma occurs almost uniquely in individuals exposed to asbestos whereas lung cancer is strongly associated with smoking. If the asbestos exposure is sufficient however, the incidence of lung cancer is higher than would be expected from the smoking effect alone. For lung cancer in asbestos workers, asbestosis is not a prerequisite for recognition as an occupation-related disease. The intensity and duration of exposure to asbestos are factors associated with higher risk of lung cancer. These factors can be estimated on the basis of the work history or, when necessary, by analyzing mineral dust from available lung tissues.

Asbestos↗

Effects of asbestos and man-made vitreous fibers on cell division in cultured human mesothelial cells in comparison to rodent cells.

We report the effects of chrysotile and crocidolite asbestos, and glass and rock wool fibers (man-made vitreous fibers, MMVF) on the induction of binucleate cells in vitro. The response of human mesothelial cells (target cells in fiber carcinogenesis) and rodent cells was compared. Human primary mesothelial cells, MeT-5A cells (an immortalized human mesothelial cell line), and rat liver epithelial (RLE) cells were exposed to asbestos and MMVF samples of similar size range. Milled glass wool, milled rock wool, and titanium dioxide were used as non-fibrous particle controls. All four fiber types caused statistically significant increases in the amount of binucleate cells in human primary mesothelial cells and MeT-5A cells (in the dose range 0.5-5.0 micrograms/cm2). Chrysotile and crocidolite asbestos were more effective (1.3-3.0-fold increases) than thin glass wool and thin rock wool fibers (1.3-2.2-fold increases). However, when the fiber doses were expressed as the number of fibers per culture area, the asbestos and MMVF appeared equally effective in human mesothelial cells. In RLE cells, chrysotile was the most potent inducer of binucleation (2.9-5.0-fold increases), but the response of the RLE cells to crocidolite, thin glass wool, and thin rock wool fibers was similar to the response of the human mesothelial cells. No statistically significant increases in the number of bi- or multinucleate cells were observed in human primary mesothelial cells or RLE cells exposed to the non-fibrous dusts. In MeT-5A cells exposed to 5 micrograms/cm2 of milled glass wool and milled rock wool, as well as in cultures exposed to 2 and 5 micrograms/cm2 of TiO2, significant increases were, however, observed. Our results show that rodent cells respond differently to mineral fibers than human cells. The results also add evidence to the suggested importance of disturbed cell division in fiber carcinogenesis.

Aneuploidy↗

Changes in lipid ordering of model phospholipid membranes treated with chrysotile and crocidolite asbestos.

A variety of inorganic particles bind to cell membranes and cause alterations in phagocytosis, migration, and metabolism leading to eventual cell death. The mechanism which mediate these events at the complex membrane level are not known. In attempting to define the mechanisms of asbestos-induced membrane changes, we have prepared small unilamellar vesicles (SUV) of dipalmitoyl phosphatidylcholine as a simplified model of the cell membrane. Negatively stained preparations for electron microscopy demonstrated that the SUVs bind to both chrysotile and crocidolite asbestos fibers. Electron spin resonance showed that both asbestos types caused increased membrane rigidity at the level of the 12th carbon, whereas chrysotile induced increased rigidity at the 5th carbon level as well. Studies using DPPC membranes compared to SUVs made of phosphatidylcholine from egg yolk support the view that lipid peroxidation may play no significant role in alterations of membrane rigidity induced by the asbestos particle binding. Similar alterations of membrane rigidity and lipid peroxidation at the depth of the 12th carbon have been reported in complex naturally occurring erythrocyte membranes. This suggests that our observations may be relevant to biological membranes and that the model system of SUVs is appropriate for additional studies on the mechanisms of particle-induced membrane injury.

Animals↗

Asbestos-derived reactive oxygen species activate TGF-beta1.

Transforming growth factor-beta1 (TGF-beta1) is a potent peptide that inhibits epithelial and mesenchymal cell proliferation and stimulates the synthesis of extracellular matrix components. This cytokine is produced in a biologically latent complex bound to a latent-associated peptide (LAP), and it is the disassociation of this complex that regulates TGF-beta activity. A number of mechanisms have been shown to activate TGF-beta1. We show here that reactive oxygen species (ROS), generated by the iron in chrysotile or crocidolite asbestos, mediate the biological activity of TGF-beta1. Recombinant human latent TGF-beta1 was activated in a cell free system in the presence of asbestos and ascorbic acid. Latent TGF-beta1 was overexpressed in both A549 and mink lung epithelial cell lines through an adenovirus vector containing the full-length construct for porcine TGF-beta1. This latent TGF-beta1 was activated in a concentration-dependant fashion by introducing asbestos into the cell cultures. This activation was reduced significantly through the use of superoxide dismutase, catalase or deferoxamine. Amino-acid constituents of the LAP were oxidized as demonstrated by the appearance of carbonyls detected by Western analysis. The oxidized LAP could no longer form a complex with TGF-beta1. Our data support the postulate that ROS derived from asbestos provide a mechanism for activating TGF-beta1 in the alveolar environment by oxidizing amino acids in LAP.

Animals↗

A comparison of asbestos and urban particulate matter in the in vitro modification of human alveolar macrophage antigen-presenting cell function.

The mechanism for how inhaled particles cause or exacerbate human diseases is not known. It is clear, however, that some particles are more bioactive than others. One possible mechanism may involve a modification of antigen-presenting cell function. In this study, 2 forms of asbestos (crocidolite and Libby amphibole) and PM(2.5) (an urban particle) were cultured with human alveolar macrophages (HAMs) to determine whether antigen-presenting cell (APC) function was altered. HAMs were exposed to the bioactive particles, asbestos and PM(2.5), for 24 hours, then isolated free of extracellular particulates and nonviable cells. Isolated HAMs were then cultured with autologous lymphocytes in an 11-day APC assay using tetanous toxoid as the antigen and the resulting culture supernatants were assayed for lymphocyte-derived cytokines. Asbestos exposure, regardless of type, up-regulated a TH1 lymphocyte-derived cytokine, interferon gamma (IFNgamma), and the TH2 lymphocyte-derived cytokines interleukin-4 (IL-4) and interleukin-13 (IL-13). PM(2.5) exposure up-regulated all 3 cytokines also. Although cytokine production levels were significantly higher for the treatment compared to control cultures as a group, there was extreme variability in the responses between subjects. In addition, there was no correlation between an individual's cells' response to asbestos verses PM, suggesting that more than one possible mechanism exists for a particle-induced APC effect and individual differential sensitivities to inhaled bioactive particles. This work supports the hypothesis that some inhaled particles can modify immune function by directly affecting APCs thus up-regulating the normal lymphocyte response to antigens in the lung.

Air Pollutants↗

The classification of asbestos fibres by scanning electron microscopy and computer-digitizing tablet.

Because of the need to completely and accurately size asbestos bulk samples for toxicity studies, a method was developed to classify asbestos fibres using enlarged micrographs originally produced on the scanning electron microscope (SEM). Individual fibre length and width measurements were performed on a computer-assisted, digitizing tablet. This method, though time consuming, permitted the sizing of all fibres (length and width) and particles (area) in selected fields of view at SEM magnifications of x100 and x2500. Final enlargement of the micrographs permitted sizing magnifications of x10,000. Seven distinct asbestos samples were classified including five chrysotile and two crocidolite samples. Statistical analyses showed good interfilter fibre size correlation for all types of asbestos. In addition, it was determined that a representative sizing of all fibres and non-fibrous particles on a filter preparation could be performed using five sets of micrographs taken at a magnification of x2500 and enlarged to x10,000: an inverse square root transformation (-0.5 power) is needed to normalize the distributions of length and width.

Analysis of Variance↗

Assessment of environmental asbestos exposure in Turkey by bronchoalveolar lavage.

Environmental or domestic exposure to asbestos fibers originating from local soil is responsible for a high incidence of diseases in large rural areas of Turkey. Bronchoalveolar lavage fluids (BALF) were obtained for 65 Turkish subjects originating from these areas and for 42 Turkish controls. Asbestos bodies (ABs) and uncovered fibers (UFs) were quantified by phase contrast light microscopy. Total fiber burden was determined by transmission electron microscopy. The main asbestos types disclosed were tremolite and to a lesser extent chrysotile. AB and fiber concentrations were higher in environmentally exposed subjects (geometric mean [geometric standard deviation]: 5.20 [6.22] AB/ml, 444 [11.6] tremolite fibers/ml) than in control subjects (0.22 [1.45] AB/ml, 12.0 [15.4] tremolite fibers/ml) (p < 0.001). In subjects environmentally exposed in Turkey, AB burdens on tremolite were in the same range as those on commercial amphiboles in subjects occupationally exposed in Belgium. In Turkish subjects, values above either 1 AB/ml, 3 uncovered fiber/ml in light microscopy, or 300 fibers/ml in electron microscopy indicated usually an abnormal alveolar retention reflecting a significant cumulative exposure from environmental or domestic origin. These observations are probably valid for other areas in the world where diseases associated with environmental exposure to soil- derived asbestos fibers occur and for immigrants originating from these areas.

Adult↗

Cytotoxic effect of asbestos on macrophages in different activation states.

The in vitro effects due to phagocytosis of asbestos by mouse peritoneal macrophages in various stages of activation have been compared. The amphiboles proved relatively inert; chrysotile, however, expressed a greater degree of cytotoxicity toward those populations of macrophages induced in vivo with asbestos, than toward any of the other populations of cells. These results are compared with data concerning the enzyme release from the different populations of macrophages following phagocytosis of asbestos. The results indicate that those macrophages that have been exposed to a prior stimulation of either amphibole or serpentine asbestos in vivo are particularly sensitive to exposure to a second dose of a toxic fiber.

Animals↗

Mortality among asbestos-exposed workers in a railroad workshop.

The mortality experience of a cohort of 3 297 railroad maintenance shopworkers exposed to asbestos was investigated. The study period was 1951-1980, and the vital status was assessed for 99.6% of the men. Individual estimates of cumulative asbestos exposure were based on detailed records on work tasks and divisions. Dust measurements were scanty in earlier decades, and estimates of average fiber levels were therefore based on information on the amount and kind of asbestos used, job descriptions, and interviews with older workers. The overall mortality was lower than expected from the national death rates (standardized mortality ratio = 82). The mortality from lung cancer increased as cumulative exposure increased in consistent dose-response relationships. Employment times of less than 30 years in workplaces with moderate levels of mainly chrysotile asbestos was not associated with any apparent increase in the risk of lung cancer. A subgroup exposed for more than 30 years in workplaces repairing steam engines, where amphiboles were used as well, had a standardized mortality ratio of 192 for lung cancer. This figure may be an underestimation due to healthy worker selection and fewer smokers than normal. The "true" standardized mortality ratio was estimated to be about 300. Five cases of mesothelioma were observed.

Aged↗