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Kerosene soot genotoxicity: enhanced effect upon co-exposure with chrysotile asbestos in Syrian hamster embryo fibroblasts.

Epidemiological and experimental studies have suggested an enhancement of asbestos-induced bronchogenic carcinoma by cigarette smoke. Further, our recent experimental and epidemiological studies have indicated that besides smoking, several other compounds including kerosene soot may accelerate disease processes in asbestos-exposed animals as well as in the humans. Incomplete combustion of kerosene oil generates large volumes of soot, which contains various polycyclic aromatic hydrocarbons and aliphatic compounds. As reported earlier, exposure to kerosene soot is known to cause biochemical and pathological changes in the pulmonary tissue, which may cause cardiopulmonary disorders. In this study we investigated genotoxic effects caused by kerosene soot and chrysotile asbestos as well as co-exposure of kerosene soot and chrysotile using Syrian hamster embryo fibroblasts (SHE). The micronucleus assay revealed a significant increase of induced micronuclei (MN), (P</=0.05) in SHE cells after treatment with kerosene soot (0.5-1.0 microg/cm(2)) for 66 h (36 MN/1000 cells). Combined treatment with chrysotile and soot induced up to 110 MN/1000 cells (chrysotile alone: 80 MN/1000 cells; concentrations: 1 microg/cm(2), exposure times: 66 h). Kinetochore staining revealed mainly clastogenic effects in all cases (soot: 21.3% CRMN(+); chrysotile: 27%; soot+chrysotile: 27.6%; control: 20.8%). This is the first study showing that kerosene soot is not only genotoxic but it can also elevate the genotoxic potential of chrysotile asbestos. This information may be of importance for workers occupationally exposed to asbestos and domestically exposed to kerosene soot.

Animals↗

[Asbestos-related pleuropulmonary diseases: pictorial essay].

Pleural and pulmonary asbestos-related diseases range from benign conditions, like pleural effusion and pleural plaques, to some neoplasias, such as lung cancer and malignant mesothelioma. Pleural effusion is the earliest finding after asbestos exposure, but the imaging findings are not specific. Diffuse pleural thickening involves the visceral pleura and pleural plaques are considered to be hallmarks of exposure. Asbestosis is the pulmonary fibrosis due to asbestos. Rounded atelectasis is a peripheral lung collapse in these individuals, generally related to pleural disease. Some neoplasias, like lung carcinoma and pleural mesothelioma, are more prevalent in asbestos-exposed subjects. The aim of this essay is to illustrate the main imaging findings of asbestos-related diseases.

Asbestos↗

Incidence of cancer among Finnish patients with asbestos-related pulmonary or pleural fibrosis.

OBJECTIVES: To study the asbestos-associated risk of lung cancer according to the histological type of cancer, the time of and time since diagnosis of asbestosis, the asbestos-associated risk for cancers other than lung cancer or mesothelioma, and the predictive value of asbestos-related pleural abnormalities as regards the risk of cancer. METHODS: Finnish patients with asbestosis (n = 1,376) or asbestos-related benign pleural disease (n = 4,887) notified as an occupational disease since 1964 were followed-up through the Finnish Cancer Registry for cancer in 1967-95. RESULTS: Compared with the total cancer incidence in Finland, men with asbestosis had a raised risk of lung cancer (standardized incidence ratio [SIR] = 6.7; 95% confidence interval [CI] = 5.6-7.9), mesothelioma (SIR = 32, CI = 14-60) and cancer of the larynx (SIR = 4.2, CI = 1.4-9.8). The risk of lung cancer was similarly raised for all histological types of lung cancer (the highest in insulators) and did not change markedly over time of notification or duration of follow-up. Men with benign pleural disease had a raised risk of mesothelioma (SIR = 5.5, CI = 1.5-14) and a slightly elevated risk of lung cancer (SIR = 1.3, CI = 1.0-1.8). Among women with asbestosis, significant excess was found for lung cancer and mesothelioma. CONCLUSION: Asbestosis and asbestos-related benign pleural disease seem to possess different predictive values as regards the risk of lung cancer.

Adult↗

Cancer in asbestos-exposed occupational cohorts: a meta-analysis.

OBJECTIVE: To examine existing asbestos-exposed occupational cohorts and apply a meta-analytic technique to determine the magnitude of association between exposure and lung cancer and to investigate other cancer sites that may be related to such an exposure. METHODS: We summarized the data from 69 asbestos-exposed occupational cohorts reporting on cancer morbidity and mortality. Data were extracted regarding numbers of deaths for each cancer, numbers of mesotheliomas, occupations and latency for respiratory, gastrointestinal, urinary and lymphohematopoietic cancers. For each cancer, we calculated a meta-SMR and examined heterogeneity of results using a chi-square test and by calculating a Z-statistic for each study. To examine the dose-response effect, we divided the studies into tertiles according to the percentage of mesothelioma deaths that served as a proxy estimation of asbestos exposure. RESULTS: Lung cancer data demonstrated meta-SMRs of 163 and 148 with and without latency, respectively, with significant heterogeneity of results even after stratification according to occupational groups. Stratification of lung cancer studies according to percentage of mesothelioma deaths showed a dose-response effect. Z-scores ranged from -12.21 to + 29.49. Analysis for laryngeal cancer yielded meta-SMRs of 157 and 133 with and without latency, respectively, demonstrating homogeneous results across studies but accompanied by no evidence of a dose-response effect. Data for gastrointestinal cancers showed no evidence of a significant association and no dose-response effect. Kidney cancer demonstrated statistically non-significant meta-SMRs of 120 (95% CI 88-160) and 111 (95% CI 94-131) with and without latency respectively. CONCLUSIONS: This meta-analysis demonstrates a wide variability of the association between occupational asbestos and lung cancer. There was a suggestion of an association between asbestos and laryngeal carcinoma and no clear association with other cancers.

Adult↗

A one-generation cluster of malignant mesothelioma within a family reveals exposure to asbestos-contaminated jute bags in Naples, Italy.

Substantial evidence supports the role of asbestos in malignant mesothelioma. Clustering for this malignancy among relatives not only suggests genetic susceptibility as a relevant component but also provides a clue to investigate non-occupational sources of exposure. We identified five cases of malignant mesothelioma within one family with exposure to asbestos experienced during childhood, as 'next door' residents of a workshop recycling asbestos-contaminated jute sacks in Naples, Italy. This cluster discloses the health risk in the reuse of bags that previously had contained asbestos. Furthermore, it emphasizes the role of asbestos in the genetic-environmental interaction issue of malignant mesothelioma.

Adult↗

Asbestos-catalysed lipid peroxidation and its inhibition by desferroxamine.

In an effort to understand the properties of asbestos fibres that might contribute to their being toxic, we incubated three different varieties of asbestos with phospholipid emulsions and looked for evidence of lipid peroxidation. Although all three types of asbestos were able to catalyse lipid peroxidation in the native state, this catalytic activity was inhibited by pre-washing of the asbestos with the iron chelator desferroxamine. This suggests that: lipid peroxidation may be one of the mechanisms by which asbestos produces tissue injury, and treatment with iron chelators might diminish the potential to produce this injury.

Adenosine Diphosphate↗

Asbestos-induced pleural diseases--thoracoscopic aspects.

The endoscopic morphology of asbestos-induced pleural disease is demonstrated by typical thoracoscopic findings. Among 627 thoracoscopies, lesions induced by exposure to asbestos were found in 9.9% (50 malignant mesotheliomas of the pleura, 10 pleural hyalinoses, 2 asbestos pleurisies). This comparatively high percentage is indicative of the pathogenic relevance of asbestos in the pleuropulmonary region. In addition to describing the diffuse malignant mesotheliomas of the pleura, reference is made in the discussion to the possible occurrence of benign localized fibromatous mesotheliomas that are not clearly related to asbestos exposure.

Aged↗

[Legal cases on the correlation between exposure to asbestos fiber dust and laryngeal cancer].

In Germany the causal relationship between laryngeal carcinoma and occupational exposure to asbestos is under discussion. We report on 30 cases of laryngeal carcinoma for which compensation was considered, since an occupational contact with asbestos was confirmed or suspected. We looked especially for signs of non-tumorous lesions related to asbestos exposure in radiography or CT of the chest. Such signs could be detected in 12 individuals. In Germany compensation for an occupational disease can be granted only, if e.g. the relevance of asbestos exposure is sufficiently probable, with special regard to other noxious influences such as cigarette abuse. Asbestosis of the larynx cannot be diagnosed specifically; we, therefore suggest proving the relevance of asbestos exposure in respect of signs of tumorous or non-tumorous lesions in the chest.

Aged↗

Asbestos induces nuclear factor kappa B (NF-kappa B) DNA-binding activity and NF-kappa B-dependent gene expression in tracheal epithelial cells.

Nuclear factor kappa B (NF-kappa B) is a transcription factor regulating expression of genes intrinsic to inflammation and cell proliferation--features of asbestos-associated diseases. In studies here, crocidolite asbestos caused protracted and dose-responsive increases in proteins binding to nuclear NF-kappa B-binding DNA elements in hamster tracheal epithelial (HTE) cells. This binding was modulated by cellular glutathione levels. Antibodies recognizing p65 and p50 protein members of the NF-kappa B family revealed these proteins in two of the DNA complexes. Transient transfection assays with a construct containing six NF-kappa B-binding DNA consensus sites linked to a luciferase reporter gene indicated that asbestos induced transcriptional activation of NF-kappa B-dependent genes, an observation that was confirmed by northern blot analyses for c-myc mRNA levels in HTE cells. Studies suggest that NF-kappa B induction by asbestos is a key event in regulation of multiple genes involved in the pathogenesis of asbestos-related lung cancers.

Animals↗

Asbestos, smoking, and laryngeal carcinoma.

This study was designed to examine the relationship between exposure to asbestos and laryngeal cancer. A retrospective study of 43 pairs of patients with laryngeal cancer and their matched controls examined a number of variables, including smoking, exposure to asbestos, and other occupational factors. Patients with laryngeal cancer and the controls were matched for age, sex, and place of residence. The data indicate a substantial association between asbestos exposure and laryngeal cancer. Cigarette smoking was also associated with the disease, although the strength of association was not as high as that for asbestos. Exposure to uranium, chromium, nickel, cobalt, arsenic, x-rays, and alcohol did not appear related to later development of carcinoma of the larynx. We conclude that exposure to asbestos and cigarette smoking are potent factors in the development of this disease.

Adult↗

Mesothelioma and asbestos in the Province of Quebec, 1969-1972.

All records of patients who died of mesothelioma in the Province of Quebec during the period 1969-1972 were collected and reviewed. Asbestos exposure in this group was compared with that in two control groups, one of persons dying of accidental causes and the other of those dying of cardiovascular disease. The mortality rate for mesothelioma was estimated at between 2.3 and 2.8 per million per year. Men were affected twice as frequently as women, this difference being related exclusively to pleural mesothelioma. The incidence in urban regions was much higher than in rural areas, and areas involved in mining showed an incidence in the expected range. Thirty-four percent of the patients with mesothelioma and only 2% of controls had histories of direct exposure to asbestos. This exposure was related to asbestos processing and not its production. No woman gave a history of occupational exposure to asbestos. It appeared that chrysotile may be less related to the production of mesothelioma than other types of asbestos fibers.

Asbestos↗

Environmental asbestos exposure and cancer mortality.

From 1970 to 1980, mortality from cancer of the lung and stomach was analyzed in a town with asbestos deposits and in a town with asbestos processing. The populations of the entire country, the province, the district, and of all communities of the same size and agricultural index were used as references. In the town with asbestos contamination of air and water from natural tremolite deposits and an endemic occurrence of pleural plaques, no increased risk for lung or stomach cancer was found. In the town with asbestos cement production lung cancer rates were lower in males and higher in females, and stomach cancer rates were lower than expected. No significant differences could be attributed to environmental asbestos exposure.

Asbestos↗

Asbestos body formation in the human lung: distinctions, by type and size.

The fraction of fibers coated in a total of 3,800 asbestos fibers from 38 patients with disease related to asbestos (100 fibers per patient) was determined, according to asbestos fiber type and size parameters. Among the 3,800 fibers, 638 (16.8%) were coated and 3,162 were uncoated. All fibers were analyzed at 2,000 x magnification (lower limit of detection: 2 microns for length and 0.06 microns for diameter). The diameter of the totally coated fibers (28.4% of total bodies; 181/638) was not measured. The percentage of coated fibers varied with the asbestos type; it was 27.1% (335/1235) for amosite fibers, 16.0% (228/1423) for crocidolite, 6.6% (60/908) for tremolite or actinolite, 6.5% (14/214) for anthophyllite, and 5% (1/20) for chrysotile fibers. Most coated fibers were longer than 10 microns and had an aspect ratio (length/diameter) of more than 20. Approximately 60% of coated fibers had an aspect ratio of more than 100. The longer the fiber, the greater the percentage of coated fibers, regardless of diameter. The increase in the percentage associated with length was more marked in fibers with a smaller diameter; the percentage of coated fibers was, therefore, greater in fibers 30 microns or less in diameter. However, in fibers longer than 30 microns, the relationship to percentage of coated fibers was not as clear, and the diameter was less important. Accordingly, the fibers with high aspect ratios, particularly long fibers, tended to show asbestos body formation. The percentage of long fibers was highest in amosite, and the percentage of fibers with an aspect ratio of more than 100 was highest in amosite and crocidolite.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Malignant mesothelioma and occupational exposure to asbestos: a clinicopathological correlation of 1445 cases.

Asbestos exposure is indisputably associated with development of mesothelioma. However, relatively few studies have evaluated the type of occupational exposure in correlation with asbestos fiber content and type. This study reports findings in 1445 cases of mesothelioma with known exposure history; 268 of these also had fiber burden analysis. The 1445 cases of mesothelioma were subclassified into 23 predominant occupational or exposure categories. Asbestos body counts per gram of wet lung tissue were determined by light microscopy. Asbestos fiber content and type were determined by scanning electron microscopy and energy dispersive x-ray analysis. Results were compared with a control group of 19 lung tissue samples. Ninety-four percent of the cases occurred among 19 exposure categories. Median asbestos body counts and levels of commercial and noncommercial amphibole fibers showed elevated levels for each of these 19 categories. Chrysotile fibers were detectable in 36 of 268 cases. All but 2 of these also had above-background levels of commercial amphiboles. When compared to commercial amphiboles, the median values for noncommercial amphibole fibers were higher in 4 of the 19 exposure groups. Most mesotheliomas in the United States fall into a limited number of exposure categories. Although a predominant occupation was ascertained for each of these cases, there was a substantial overlap in exposure types. All but 1 of the occupational categories analyzed had above-background levels of commercial amphiboles. Commercial amphiboles are responsible for most of the mesothelioma cases observed in the United States.

Adolescent↗

The sensitivity of lavage analysis by light and analytical electron microscopy in correlating the types of asbestos from a known exposure setting.

Lavage material was collected from 12 individuals whose work history included working in a cement manufacturing facility. The manufacturing processes of the facility included the use of crocidolite and chrysotile asbestos. Lavage material was prepared via digestion procedure and then analyzed for the presence of ferruginous bodies by light microscopy and for uncoated asbestos fibers by analytical transmission electron microscopy. A comparison was made as to the sensitivity between two analytical methods for linking a past exposure to a specific type of asbestos. The use of analytical transmission electron microscopy for identification of core material in the ferruginous bodies as well as for quantification of the uncoated asbestos fibers increased the sensitivity of the information obtained from lavage samples as necessary for confirming exposure in the past to specific types of asbestos.

Adult↗

Community exposure to asbestos from a vermiculite exfoliation plant in NE Minneapolis.

Western Mineral Products/W. R. Grace operated a vermiculite plant in a mixed industrial/residential area of northeast Minneapolis from 1936 to 1989. The plant processed vermiculite ore contaminated with amphibole asbestos from a mine in Libby, MT. Air monitoring in the early 1970s found fiber concentrations in excess of 10 fibers per cubic centimeter of air (f/cc), indicating that worker exposure to asbestos was occasionally 100 times the current occupational standard. Residents of the surrounding community also had direct contact with vermiculite processing wastes (containing up to 10% amphibole asbestos) that were made freely available. Children played on waste piles and neighborhood residents hauled the wastes away for home use. In total, 259 contaminated residential properties have been found to date. Reported emission factors and plant process data were used as inputs to model airborne emissions from the plant over several operating scenarios using the U.S. Environmental Protection Agency (EPA) ISC-Prime model. Results estimate short-term air concentrations of asbestos fibers in residential areas nearest the plant may have at times exceeded current occupational standards. Exposure estimates for other pathways were derived primarily from assessments done in Libby by the U.S. EPA. The Northeast Minneapolis Community Vermiculite Investigation (NMCVI) was conducted by the Minnesota Department of Health to identify and characterize the exposures of a cohort of over 6000 people who live or lived in Northeast Minneapolis and may have been exposed to asbestos. This cohort is now being investigated in a respiratory health screening study conducted by the University of Minnesota and the Minnesota Department of Health.

Aluminum Silicates↗

Asbestos burden in two cases of mesothelioma where the work history included manufacturing of cigarette filters.

Asbestos has been used in many applications, but possibly one of the more unique was in the manufacturing of filters for cigarettes. The type of asbestos used in this application was crocidolite. Data from several resources indicate that crocidolite was one of the least utilized types of commercial asbestos in the United States. The present study provides quantitative tissue burden analysis data for two mesothelioma cases where the work histories included manufacturing of cigarette filters that contained crocidolite. The data include the number of asbestos bodies and uncoated fibers per gram of tissue, as well as the dimensions of these structures. The conclusion of the findings indicates that the individuals had an appreciable homogeneous exposure to crocidolite asbestos.

Aged↗

Asbestos induces tissue factor in Beas-2B cells via PI3 kinase-PKC-mediated signaling.

Treatment of Beas-2B airway epithelial cells with crocidolite asbestos induced tissue factor (TF) mRNA and TF-dependent procoagulant activity. The mitogen-activated protein kinase (MAPK) inhibitors UO126 and SB203850 decreased TF expression in both naive and crocidolite-treated Beas-2B cells to the same extent. Calphostin, an inhibitor of classical and novel protein kinase C (PKC) isotypes, reduced TF mRNA in both intact and crocidolite-treated Beas-2B cells by about 50%. Conversely, the phosphatidylinositol 3-kinase (PI3 kinase) inhibitor LY294002 and a selective PKCzeta inhibitory peptide decreased TF mRNA expression in asbestos-treated cells to a greater extent than in naive cells, suggesting that signaling via this pathway contributes to asbestos-induced TF expression. These results demonstrate that crocidolite asbestos induces TF expression by Beas-2B cells and suggest that the process involves the PI3 kinase-PKCzeta signaling pathway, representing a newly recognized potential mechanism by which asbestos may contribute to lung remodeling.

Asbestos, Crocidolite↗