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An activating and cytotoxic effect of asbestos on polymorphonuclear leukocytes.

Chrysotile asbestos induces extensive enzyme release from polymorphonuclear leukocytes (PMNs). The release of the cytoplasmic enzyme lactate dehydrogenase implies membrane damage and cytotoxicity. In the presence of extracellular Ca2+ asbestos exerts an activating effect, evident from the release of granule-associated enzymes by exocytosis. Both the cytotoxic and activating effect of asbestos may contribute to asbestos-induced tissue damage.

Animals↗

Asbestos as reference material for fibre-induced cancer.

The objective of this paper is to review published data on the carcinogenicity of asbestos fibres with regard to the elucidation of a potential risk originating from exposure to man-made vitreous fibres (MMVF). Steps in the comparison of the two fibre classes are characterization of the fibres, pulmonary deposition, biodurability and biopersistence and a review of the cancer risk from asbestos fibres after inhalation in rats and humans. Various dust samples of chrysotile, crocidolite, and amosite were used as reference materials in studies with experimental animals. These fibres are normally thinner and shorter than MMVF. These differences in dimensions cause differences in the deposition in the airways. In addition, significant dissimilarities exist in the deposition pattern between rats and humans. Data from biopersistence studies show that focusing only on fibres longer than 20 microm and using weighted half-time for a characterization of risk may be misleading. Inhalation experiments with rats need fibre exposure concentrations over 100 times higher to match the lung cancer risk of asbestos workers, and about 1,000 times higher to reach the same mesothelioma risk. Also, the striking difference between the low lung burden of amphibole fibres of asbestos workers with mesothelioma and the more than 1,000 times higher lung burden of rats with a low mesothelioma risk demonstrates the low sensitivity of the inhalation test model for the carcinogenic potency even of crocidolite fibres. It can be concluded that the rat inhalation model is also not sensitive enough to predict the cancer risk of other fibre types for humans.

Adult↗

Mesotheliomas among Italians, returned to the home country, who worked when migrant at a cement-asbestos factory in Switzerland.

OBJECTIVES: To report the occurrence of mesotheliomas in Italy among subjects who worked, when migrant, at a cement-asbestos factory in Niederurnen, Switzerland, and had resettled to the home country. METHODS: Information about the disease and on the working history of subjects was collected by regional mesothelioma registries. Only cases diagnosed by means of histo-pathological examinations have been considered here. RESULTS: 15 mesotheliomas (13 pleural, 2 perithoneal; 12 among males, 3 among females) have been identified among Italians, who had worked at the factory. None of them had other occupational exposure to asbestos. The majority was living in the Veneto Region (North East of Italy), and in Puglia (Southern Italy). CONCLUSIONS: Exposure to asbestos at this factory has already caused an important number of occupational cancers among the employees, a large fraction being constituted of migrants. In order to avoid under-estimation of risks and to allow compensation, diseases which occur among foreign workers returned to their home country should be evaluated. Migration for work is at the genesis of asbestos-related mesotheliomas now occurring in Italy.

Adult↗

Three decades of pleural cancer and mesothelioma registration in Austria where asbestos cement was invented.

Recently, a new mesothelioma epidemic was predicted from observations made in Western Europe. From early observations in Austria the lower increase in cases of mesothelioma compared with neighbor countries had been related to different uses of asbestos. In order to test this hypothesis, incidence and mortality of pleural cancer [International Classification of Diseases (ICD)-8/9 163] were analyzed for three decades and supplemented by data from a cohort study in the factory that had been the largest consumer of asbestos imported to Austria and from all Austrian occupational diseases registered between 1990 and 2001. In men, mortality rates (based on 15 to 45 deaths/year) were lowest in 1980-1989, but similar in 1970-1979 and 1990-2001. No increase in younger-birth cohorts was detected. Incidence rates (based on 13 to 44 cases/year) increased (36%) non-significantly ( P=0.14). In women, a significant decrease in mortality and incidence rates ( P<0.01) was observed from 1970. Rates from work-related mesothelioma (based on only 0-7 men and 0-4 women/year) must be interpreted with caution. In the cohort of 2,816 asbestos cement workers 26 pleural mesotheliomas were registered from 1990 through mid-1999. Six of these cases (three male and three female) had not been registered as an occupational disease, but all of these cases had been encoded under ICD 163 in mortality statistics. One female cohort member registered as having asbestosis according to the death certificate had died from mesothelioma according to the statistics of occupational diseases. We conclude that no epidemic of mesothelioma due to past asbestos exposure is to be expected in Austria.

Asbestos↗

Lung cancer and mesothelioma in towns with environmental exposure to asbestos in Eastern Anatolia.

OBJECTIVE: Our previous study demonstrated the presence of environmental tremolite and chrysotile asbestos fiber exposure in Hekimhan town in Malatya located in eastern Turkey. The aim of this study was to investigate whether environmental asbestos exposure increases the incidence of lung cancer and mesothelioma. METHOD: One hundred and forty-nine patients with mesothelioma and lung cancer living in the center or in the towns of Malatya were retrospectively analyzed. The Incidences of lung cancer and mesothelioma were calculated. RESULTS: The incidences of lung cancer and mesothelioma were 3.39/100,000 and 0.21/100,000, respectively, for the whole population of Malatya; while they were 8.23/100,000 and 1.45/100,000 in Hekimhan. The incidences were strikingly high (22.39/100,000 for lung cancer and 7.46/100,000 for mesothelioma) in Arguvan, another town in Malatya where an analysis for asbestos could not be performed. The overall incidence in Turkey was reported as 5.9/100,000 by the Health Ministry in 1994. The incidences of lung cancer were nearly 1.3-fold higher in Hekimhan and fourfold higher in Arguvan then in the general population of Turkey. CONCLUSION: The incidences of mesothelioma and lung carcinoma in Hekimhan were higher than those of the general population in Turkey, suggesting a role of environmental asbestos exposure in lung cancer and mesothelioma.

Adult↗

Pleural mesothelioma associated with indoor pollution of asbestos.

This case report concerns a 46-year-old woman, dying from histologically confirmed diffuse malignant mesothelioma after asbestos exposure, which was only caused by indoor pollution from crocidolite-containing spray asbestos in building materials. There was no other known occupational or environmental asbestos exposure during her life. The lung tissue fibre analysis by light microscopy showed significantly increased concentrations of ferruginous bodies (3162 FB per gram of wet lung tissue). By use of scanning transmission electron microscopy, clearly increased concentrations of amphibole fibres (8.6 x 10(6) fibres longer than 1 microm and 0.6 x 10(6) fibres longer than > or =5 microm per gram dry tissue), mainly classified as crocidolite, were observed. The disease was attributed to indoor exposure to sprayed asbestos, which occurred during her work as a decorator in the studio of a warehouse.

Air Pollution, Indoor↗

Observations on the distribution of asbestos fibers in human lungs.

In an attempt to begin evaluating the distribution of mineral fibers within lung, multiple small adjacent samples were selected from peripheral portions of three normal and six asbestotic lungs, and analyzed for asbestos and nonasbestos fiber content. For both normal and fibrotic lungs there was marked variation in fiber concentration from site to site; the mean in-case ratio of maximum to minimum fiber concentration was 7.5 for amosite and crocidolite, 7.0 for tremolite, 3.8 for chrysotile, 4.0 for nonasbestos fibers, and 5.4 for asbestos bodies. In order to test the precision of the membrane filter method of quantitating particulates, multiple replicate samples of reference mineral standards were examined in a similar fashion; for these standard samples the ratio of maximum to minimum particle concentration varied from only 1.3 to 1.5. It is concluded that: (1) the membrane filter preparation technique used here for counting fibers provides reproducible results, and (2) there is marked variation in asbestos and nonasbestos fiber concentration from area to area within lung tissue. The latter finding implies that analysis of small subpleural lung biopsies may produce misleading results, and that larger pieces or several pieces should be analyzed when attempting to define total asbestos fiber content of the lung.

Asbestos↗

Mesothelioma in pet dogs associated with exposure of their owners to asbestos.

Pet dogs with spontaneous mesothelioma were used to identify environmental exposures that might increase their owner's risk of asbestos-related disease. These animals share man's domicile environment, yet do not indulge in activities (e.g., smoking, working) which confound interpretation of epidemiologic studies. Eighteen histologically confirmed canine mesotheliomas were diagnosed at the Veterinary Hospital of the University of Pennsylvania, Philadelphia, from April 1977 to December 1981. Sixteen owners of cases and 32 owners of age, breed, and sex-matched controls were interviewed to determine their occupation and medical history and their dog's medical history, life style, diet, and exposure to asbestos. An asbestos-related occupation or hobby of a household member and use of flea repellents on the dog were significantly associated with mesothelioma. In addition, there was a trend indicating an increased risk of mesothelioma with an urban residence. Lung tissue from three dogs with mesothelioma and one dog with squamous cell carcinoma of the lung had higher levels of chrysotile asbestos fibers than lung tissue from control dogs. These findings indicate that well-designed epidemiological studies of spontaneous tumors in pet animals may provide insight into the role of environmental factors in human cancers and serve as a valuable sentinel model to identify environmental health hazards for humans.

Animals↗

The influence of amosite asbestos exposure on lung permeability.

The effect of amosite asbestos on permeability of the blood/air barrier in the lung was studied using an acute animal model. The ultrastructural tracer selected for the study was horseradish peroxidase which was given intravenously in animals that had been exposed intratracheally to asbestos. The acute period of study was either 1/2, 1, 2, 3, or 4 hr, or 1-7 or 14 days postexposure. The barrier in the normal lung was at the level of the alveolar epithelial lining. Leakage of exudate and tracer occurred through the altered barriers following asbestos exposure and the extent of leakage related directly to the degree of alveolitis and the asbestos present in the area. A trend toward recovery of the barrier occurred with the reestablishment of a more normal-appearing epithelial lining during the second week postexposure.

Animals↗

Migration of ingested asbestos.

Tissue samples from one test and one control baboon were analyzed by transmission electron microscopy for the presence of chrysotile and crocidolite asbestos. The test animal had been gavaged with cumulative doses of 800 mg each of chrysotile and crocidolite asbestos. An earlier evaluation of these tissues led to the conclusion that ingested asbestos fibers do not penetrate the gastrointestinal tract of the baboon and migrate systemically. However, the present study involved more sensitive methodology, and penetration and migration were clearly demonstrated by the recovery of significant levels of asbestos from test stomach, heart, spleen, pancreas, and blood samples.

Administration, Oral↗

Asbestos and colorectal cancer.

Reports in the literature on 21 cohorts of workers exposed to asbestos were reviewed and analyzed to determine whether there is a causal association between asbestos and colorectal cancer. The latest report up to 1988 was used for each cohort. The end point was the standardized morbidity or mortality ratio as the measure of relative risk. Two additional cohorts using mortality as the end point were excluded because the authors failed to use comparable diagnostic methods for the asbestos-exposed populations and controls. The summary standardized morbidity or mortality ratio for all 21 cohorts was 0.97 (P greater than 0.05), and there was no dose-response relationship in the two studies with such data. The evidence does not meet the established criteria for making a judgment that there is a causal relationship between asbestos and colorectal cancer.

Asbestos↗

The costs and effects of screening for cancer among asbestos-exposed workers.

Several million workers previously exposed to asbestos are at risk each year for developing asbestosis or cancer as a result of this exposure. We have reviewed the data on the general effectiveness of screening for the two most common cancers found in these workers (lung cancer and colo-rectal cancer) and have compared the relative benefits expected from screening workers for colon or lung cancer 10, 15, 20 or 25 yr after their initial exposure. Although lung cancer is common, there is little evidence at present that screening for this disease is effective in reducing mortality. Colon cancer is less common, there is more evidence that screening is effective, and the relatively high risk of dying from this disease in asbestos workers makes screening useful. The cost per additional year of life extended by screening is only a few hundreds of dollars, making colon cancer screening programs for asbestos workers considerably more cost-effective than most other screening programs. We conclude that occupational safety agencies should consider implementing screening programs for colon cancer in workers exposed to asbestos over 10 yr ago.

Asbestos↗

Asbestos and glass fibres in bacterial mutation tests.

Asbestos fibres are carcinogenic in man and experimental animals but fine glass fibres are known, at present, only to be carcinogenic in experimental animals. Asbestos and glass fibres have been studied in mutation tests using auxotrophic strains of Escherichia coli and Salmonella typhimurium. The mutagenic activities of the positive control mutagens ultraviolet light, potassium chromate, ethyl methanesulphonate and benzo(a)pyrene were detected in the experiments. However, no mutagenic activity was found to be associted with any of the asbestos and glass fibres tested over a wide range of concentrations. The implications of these findings for the mode of action of asbestos and glass fibres as carcinogens are discussed.

Asbestos↗

Genetic effects of crocidolite asbestos in Chinese hamster lung cells.

Chinese hamster lung cells cultured in the presence of crocidolite asbestos displayed inhibition of cell growth. Cell death was directly associated with the phagocytosis of larger fibres as observed with the aid of trypan blue. Water soluble components of crocidolite did not appear to inhibit cell growth. Chromosomal aberrations were induced by the asbestos. The aberrations were confined mainly to structural aberrations--breaks and fragments. Electron-microscopic preparation indicated that asbestos was readily contained in phagosomes. Phagocytosed asbestos appeared to be a weak mutagen in its ability to induce gene mutation at the hypoxanthine-guanine phosphoribosyl transferase locus.

Asbestos↗

Minimal pathologic changes of the lung and asbestos exposure.

A group of 199 autopsy subjects was investigated for minimal pathologic pulmonary changes possibly resulting from asbestos exposure. According to the standards proposed by the Pneumoconiosis Committee of the College of American Pathologists, features consistent with asbestosis grade 1 (AG1) include findings of bilateral pleural plaques, high concentrations of asbestos bodies (ABs) in digested lung tissue, and a history of occupational risk. Similar changes without evidence of ABs on histologic section and referred to as small airway lesions (SALs) present a less well-correlated association. In this study, SALs showed significant differences when compared with the features observed in subjects without possible asbestos-related pulmonary fibrotic changes. Minimal bronchioloalveolar fibrotic changes with concomitant presence of ABs can be considered a mild pneumoconiotic lesion (AG1), and SALs may be regarded as an additional indicator of asbestos exposure.

Aged↗

Asbestos-related fibrin formation in human plasma.

This study was designed to test the hypothesis that asbestos is responsible for the activation of clotting, for the reduction in activity of clotting factors and for the formation of fibrin when human plasma is exposed to asbestos chrysotile fibers in vitro. The recalcification time was accelerated in the early phase and was found to be greatly prolonged at 24 hours. The activated partial thromboplastin time showed marked changes at 24 hours only. One group of clotting factors, consisting of factors V, IX and X, showed the greatest decrease in their plasmatic activity. The factors least changed were factors XII and VIII; the other clotting factors were found in between these groups. Histologic examination demonstrated fibrin fibers in close proximity to the asbestos. Thus, chrysotile asbestos fibers activate clotting with the subsequent decrease in activity of some coagulation factors resulting in the formation of fibrin.

Adult↗

Amosite, chrysotile and crocidolite asbestos are mutagenic in Chinese hamster lung cells.

Chinese hamster lung cells cultured in the presence of amosite, chrysotile or crocidolite displayed inhibition of cell growth. Phagocytosis of asbestos by cells was observed. Amosite and chrysotile appeared to be twice as toxic as crocidolite based on an equal weight/volume basis. Induction of 6-thioguanine resistance was studied. After treatment at 10 microgram/cm2 for 24 h, and with a 48-h expression time, numerically the cells did not change significantly from 6-thioguanine-sensitive to 6-thioguanine-resistant for each pair of control and experimental mutation frequencies. When all data points were considered as a whole, use of Student's t-test on paired samples showed that all 3 types of asbestos were mutagenic in Chinese hamster lung cells. It was reported that benzo[a]anthracene was an organic contaminant of abestos. Used as a positive control compound, 7,12-dimethylbenz[a]anthracene was metabolized by rat-liver microsomes and was found mutagenic in Chinese hamster lung cells. Microsome activation did not increase the mutagenic potential of asbestos. These findings point to the weak mutagenic potential of asbestos. Chinese hamster lung cells phagocytize particles and are ideal materials to study mutagenesis of environmental agents that exist in a particulate form.

Animals↗

Inability of chrysotile asbestos fibers to modulate the 2-acetylaminofluorene-induced UDS in primary cultures of rat hepatocytes.

There is now growing evidence that asbestos fibers could act in association with genotoxic compounds, either as cocarcinogens or promoters, in the process of carcinogenesis. The hepatocyte/UDS assay system has been taken to advantage to investigate the capacity of fibers to modulate the effects of genotoxic compounds on the cell, as we previously demonstrated the hepatocytes can engage in phagocytosis of chrysotile fibers. Measurement of UDS was performed by a biochemical procedure involving liquid scintillation counting (LSC) of a purified DNA fraction as well as by radioautography. Both LSC and radioautography revealed that chrysotile asbestos fibers UICC B at concentrations up to 100 micrograms/ml do not elicit UDS, whereas 2-acetylaminofluorene (2-AAF) at low concentrations (0.05-0.625 micrograms/ml) significantly induces it in parallel positive controls. In an attempt to test the cocarcinogen hypothesis, cultures of hepatocytes were simultaneously exposed for 20 h to 2-AAF (0.05 and 0.25 micrograms/ml) and asbestos fibers (1 and 10 micrograms/ml) given as simple mixtures. It was found that the 2-AAF-induced UDS activity was the same whether fibers were present or not. This was observed with both UDS evaluation procedures at all concentration combinations selected. An analysis of variance applied to the data collected from several experiments confirmed that there was no significant 2-AAF-fiber interaction. Our data suggest the absence of intrinsic genotoxic properties for chrysotile fibers. They also indicate that the modulation of the cellular response to genotoxic agents by asbestos fibers is not detected under our test conditions and may require longer-term exposures to be expressed.

2-Acetylaminofluorene↗