SEARCH · PubMed Health

Results for “ASBESTOS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources

PubMed2004

After Helsinki: a multidisciplinary review of the relationship between asbestos exposure and lung cancer, with emphasis on studies published during 1997-2004.

Despite an extensive literature, the relationship between asbestos exposure and lung cancer remains the subject of controversy, related to the fact that most asbestos-associated lung cancers occur in those who are also cigarette smokers: because smoking represents the strongest identifiable lung cancer risk factor among many others, and lung cancer is not uncommon across industrialised societies, analysis of the combined (synergistic) effects of smoking and asbestos on lung cancer risk is a more complex exercise than the relationship between asbestos inhalation and mesothelioma. As a follow-on from previous reviews of prevailing evidence, this review critically evaluates more recent studies on this relationship--concentrating on those published between 1997 and 2004--including lung cancer to mesothelioma ratios, the interactive effects of cigarette smoke and asbestos in combination, and the cumulative exposure model for lung cancer induction as set forth in The Helsinki Criteria and The AWARD Criteria (as opposed to the asbestosis-->cancer model), together with discussion of differential genetic susceptibility/resistance factors for lung carcinogenesis by both cigarette smoke and asbestos. The authors conclude that: (i) the prevailing evidence strongly supports the cumulative exposure model; (ii) the criteria for probabilistic attribution of lung cancer to mixed asbestos exposures as a consequence of the production and end-use of asbestos-containing products such as insulation and asbestos-cement building materials--as embodied in The Helsinki and AWARD Criteria--conform to, and are further consolidated by, the new evidence discussed in this review; (iii) different attribution criteria (e.g., greater cumulative exposures) are appropriate for chrysotile mining/milling and perhaps for other chrysotile-only exposures, such as friction products manufacture, than for amphibole-only exposures or mixed asbestos exposures; and (iv) emerging evidence on genetic susceptibility/resistance factors for lung cancer risk as a consequence of cigarette smoking, and potentially also asbestos exposure, suggests that genotypic variation may represent an additional confounding factor potentially affecting the strength of association and hence the probability of causal contribution in the individual subject, but at present there is insufficient evidence to draw any meaningful conclusions concerning variation in asbestos-mediated lung cancer risk relative to such resistance/susceptibility factors.

Adenocarcinoma↗

PubMed2003

Occupational characteristics of cases with asbestos-related diseases in The Netherlands.

OBJECTIVE: To describe the occupational background of cases with an asbestos-related disease and to present overall mesothelioma risks across industries with historical exposure to asbestos. METHODS: For the period 1990-2000, cases were collected from records held by two law firms. Information on jobs held, previous employers, activities performed and specific products used were obtained from patients themselves or next of kin. Branches of industry and occupations were coded and the likelihood of asbestos exposure was assessed. For each branch of industry, the overall risk of mesothelioma was calculated from the ratio of the observed number of mesothelioma cases and the cumulative population-at-risk in the period 1947-1960. In order to compare mesothelioma risks across different industries, risk ratios were calculated for the primary asbestos industry and asbestos user industries relative to all other branches of industry. RESULTS: In total, 710 mesotheliomas and 86 asbestosis cases were available. The average latency period was approximately 40 yr and the average duration of exposure was 22 yr. Ship building and maintenance contributed the largest number of cases (27%), followed by the construction industry (14%), the insulation industry (12%), and the navy and army, primarily related to ship building and maintenance (5%). In the insulation industry, the overall risk of mesothelioma was 5 out of 100 workers, and in the ship building industry, 1 out of 100 workers. The construction industry had an overall risk comparable with many other asbestos-using industries (7 per 10,000 workers), but due to its size claimed many mesothelioma cases. CONCLUSION: The majority of cases with asbestos-related diseases had experienced their first asbestos exposure prior to 1960. For cases with first asbestos exposure after 1960, a shift was observed from the primary asbestos industry towards asbestos-using industries, such as construction, petroleum refining, and train building and maintenance. Due to the long latency period, asbestos exposure from 1960 to 1980 will cause a considerable number of mesothelioma cases in the next two decades.

Adult↗

PubMed2005

Estimating the number of asbestos-related lung cancer deaths in Great Britain from 1980 to 2000.

INTRODUCTION: Inhalation of asbestos fibres is known to cause two main kinds of cancer-mesothelioma and lung cancer. While the vast majority of mesothelioma cases are generally accepted as being caused by asbestos, the proportion of asbestos-related lung cancers is less clear and cannot be determined directly because cases are not clinically distinguishable from those due to other causes. The aim of this study was to estimate the number of asbestos-related lung cancers among males by modelling their relative lung cancer mortality among occupations within Great Britain in terms of smoking habits, mesothelioma mortality (as an index of asbestos exposure) and occupation type (as a proxy for socio-economic factors). METHODS: Proportional mortality ratios for lung cancer and mesothelioma for the 20-year period from 1980 to 2000 (excluding 1981) were calculated for occupational groups. Smoking indicators were developed from three General Household Surveys carried out during the 1980s and 1990s. Poisson regression models were used to estimate the number of asbestos-related lung cancers by estimating the number of lung cancer deaths in each occupation assuming no asbestos exposure and subtracting this from the actual predicted number of lung cancer deaths. RESULTS: The effect of asbestos exposure in predicting lung cancer mortality was weak in comparison to smoking habits and occupation type. The proportion of current smokers in occupational groups and average age at which they started smoking were particularly important factors. Our estimate of the number of asbestos-related lung cancers was between two-thirds and one death for every mesothelioma death: equivalent to between 11 500 and 16 500 deaths during the time period studied. CONCLUSIONS: Asbestos-related lung cancer is likely to have accounted for 2-3% of all lung cancer deaths among males in Great Britain over the last two decades of the 20th century. Asbestos-related lung cancers are likely to remain an important component of the total number of lung cancer deaths in the future as part of the legacy of past asbestos exposures in occupational settings.

Adolescent↗

PubMed1994

A protective role for T lymphocytes in asbestos-induced pulmonary inflammation and collagen deposition.

Several lines of evidence have suggested that specific (i.e., lymphocyte) immunity plays a role in chemical-induced pulmonary diseases, including asbestosis. To evaluate the influence of cell-mediated immunity in pulmonary inflammation and fibrosis evoked by asbestos fibers, we compared the effects of asbestos in immunodeficient mice (Balb/c nu/nu and severe combined immunodeficient [C3H-SCID]), immunologically normal mice of the same genetic background, and immunodeficient mice reconstituted with syngeneic T lymphocytes. Increases in lavaged cell numbers occurred in asbestos-treated immunodeficient mice compared with asbestos-treated immunocompetent or immunodeficient mice that received T lymphocytes. Differential analysis of the collected cells in treated mice demonstrated a predominantly neutrophilic infiltrate that correlated with increased levels of leukotriene B4 and prostaglandin E2. There were no significant differences between immunocompetent and athymic asbestos-treated mice in bronchoalveolar lavaged total protein. However, asbestos-treated SCID mice revealed a significant increase in protein content and lactate dehydrogenase activity compared with asbestos-treated normal mice, which did not occur in T lymphocyte-reconstituted SCID mice. Fibronectin levels were elevated in asbestos-exposed athymic mice when compared with air-exposed athymic mice or asbestos-exposed immunocompetent mice. Both asbestos-treated athymic and SCID mice showed a significant increase in total lung hydroxyproline when compared with asbestos-treated immunocompetent mice. Lung hydroxyproline was also reduced in asbestos-exposed SCID mice after T lymphocyte reconstitution and, conversely, increased in T cell-depleted Balb/c mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Role of oxidants in DNA damage. Hydroxyl radical mediates the synergistic DNA damaging effects of asbestos and cigarette smoke.

The mechanism by which cigarette smoking and asbestos exposure synergistically increase the incidence of lung cancer is unknown. We hypothesized that cigarette smoke and asbestos might synergistically increase DNA damage. To test this hypothesis we exposed isolated bacteriophage PM2 DNA to cigarette smoke and/or asbestos, and assessed DNA strand breaks as an index of DNA damage. Our results supported our hypothesis. 78 +/- 12% of the DNA exposed to both cigarette smoke and asbestos developed strand breaks, while only 9.8 +/- 7.0 or 4.3 +/- 3.3% of the DNA exposed to cigarette smoke or asbestos, respectively, developed strand breaks under the conditions of the experiment. Our experimental evidence suggested that cigarette smoke and asbestos synergistically increased DNA damage by stimulating .OH formation. First, significant amounts of .OH were detected by electron paramagnetic resonance (EPR) in DNA mixtures containing both cigarette smoke and asbestos, but no .OH was detected in mixtures containing cigarette smoke alone or asbestos alone. Second, the .OH scavengers, dimethylsulfoxide (DMSO), mannitol, or Na benzoate decreased both .OH detection by EPR and strand breaks in DNA mixtures exposed to cigarette smoke and asbestos. Third, the H2O2 scavenger, catalase, and the iron chelators, 1,10-phenanthroline and desferrithiocin, decreased both .OH detection and strand breaks in DNA mixtures exposed to cigarette smoke and asbestos. These latter findings suggest that iron contained in asbestos may catalyze the formation of .OH from H2O2 generated by cigarette smoke. In summary, our study indicates that cigarette smoke and asbestos synergistically increase DNA damage and suggests that this synergism may involve .OH production.

Asbestos↗

PubMedDate not supplied

[Tuscany mesothelioma registry (1988-2000): evaluation of asbestos exposure].

BACKGROUND: The Tuscany Mesothelioma Register (ARTMM) records pleural malignant mesothelioma cases of Tuscany residents, diagnosed by histological, cytological, or clinical (radiography or computerized tomography) examinations. The ARTMM began in 1988 and estimates mesothelioma incidence in Tuscany and collects information on past asbestos exposure of mesothelioma cases. OBJECTIVES: The aim of this paper was to describe the incidence of pleural mesothelioma cases in Tuscany and to analyse their possible past asbestos exposures. METHODS: We considered pleural mesothelioma cases recorded in ARTMM in the period 1988-2000 and interviews collected for these cases. In order to identify past asbestos exposure in the occupational and non-occupational history of patients, interviews were carried out using a standardised questionnaire. RESULTS: In the period 1988-2000, 494 pleural malignant mesothelioma cases were recorded in the ARTMM; 82% were males. In the periods 1988-1993, 1994-1997, 1998-2000 the incidence rates, standardised on the Italian population (per 100,000), were respectively 1.15, 1.57, 2.58 among males; 0.29; 0.27; 0.29 among females. Information on occupational history was collected for 418 mesothelioma patients (85% of recorded cases): 173 mesothelioma cases were directly interviewed; for 245 cases relatives or work colleagues were interviewed. Occupational asbestos exposure was ranked as certain, probable or possible in 72% of the interviewed cases (80% of males; 20% of females). Environmental and non-occupational asbestos exposure was identified in 1% of males, and 3% of females. In 24% of the interviewed cases (15% of males; 74% of females) no known asbestos exposure was identified. Occupational asbestos exposure occurred in maritime activities (shipyards, dock work, merchant and regular Navy), the building industry, railway carriage construction and maintenance, rail transport, textile industries (mainly rag sorting), electricity production, asbestos cement manufacture, chemical, iron and steel industries and in glass manufacturing. In Tuscany two areas are distinguished for their well-documented and massive use of asbestos: the coastal areas (Livorno and Massa Carrara) for maritime activities, and the areas of Pistoia and Arezzo for railway carriage construction and repair. Mesothelioma incidence rates in these areas are the highest in the whole region. CONCLUSIONS: Further investigation is needed in order to identify unknown asbestos uses and consequent exposure, in particular for females. Uncertainty as regards occurrence of asbestos exposure persists in the textile industries where the mesothelioma epidemics have not yet declined. Research hypotheses are addressed on the re-use of jute bags previously containing asbestos, therefore collection of further information on periods and methods of this recycling activity is essential.

Adult↗

PubMed1989

The interaction of asbestos and neutrophils injures cultured human pulmonary epithelial cells: role of hydrogen peroxide.

Asbestos exposure causes diffuse interstitial pulmonary fibrosis. Since alveolar epithelial cell injury is hypothesized to precede the fibrotic response in asbestosis, we investigated whether asbestos, either alone or in conjunction with neutrophils (PMNs), injured cultured human pulmonary epithelial cells (HPECs). HPEC cytotoxicity was assessed with a standard 51chromium release assay after a 16-hour incubation with asbestos and PMNs. Negligible HPEC cytotoxicity was observed after incubation with either amosite asbestos (500 micrograms/ml) or PMNs alone in serum-free media. However, incubation with both asbestos and PMNs caused significant HPEC injury, which was asbestos dose-dependent; causing 25% +/- 4% detachment and 52% +/- 8% 51chromium release with 500 micrograms/ml asbestos. The cytotoxic effects of asbestos plus PMNs were nearly completely attenuated with serum (20%) or catalase (100 micrograms/ml) but were not prevented with scavengers of superoxide anion, hydroxyl radical, or hypochlorous acid. A role for hydrogen peroxide (H2O2) in mediating HPEC injury was also suggested by the demonstration of asbestos-induced generation of H2O2 by PMNs. Furthermore, H2O2 alone (10(-4)mol/L) caused significant HPEC damage. Intimate contact between asbestos-activated PMNs and HPECs was a necessary requirement for PMN-mediated HPEC cytotoxicity. These data suggest that pulmonary epithelial cell injury is mediated in part by H2O2 release from asbestos-activated PMNs as well as intimate contact between the epithelial cell, PMNs, and asbestos.

Asbestos↗

PubMed1998

Current and historical American asbestos regulations.

Asbestos, and asbestos-containing materials, are subject to regulation in the USA by both the federal government and each of the 50 state governments. This paper summarizes the federal government asbestos regulations which apply to the use of asbestos, asbestos-containing products, and asbestos fiber releases, in the workplace and in the ambient environment through the USA. Regulations by the 50 states apply only within the jurisdiction of each state and, to a large extent, mimic those of the federal government. The state regulations are not discussed in this paper. The principal American government agencies that deal with asbestos regulation are the Occupational Safety and Health Administration (OSHA) and the Environmental Protection Agency (EPA). Generally, OSHA regulations apply to regulate asbestos exposures, and potential asbestos exposures, in the occupational workplace while EPA regulations apply to asbestos exposures, and potential asbestos exposures, in the nonoccupational setting. Both agencies set regulatory levels for allowable asbestos exposure. Those levels have changed, in a decreasing progression, since their enactment in the early 1970s. This paper discusses those levels and traces their progression over time.

Asbestos↗

PubMed2003

Quantitative analysis of asbestos burden in women with mesothelioma.

BACKGROUND: Lung tissue from 15 women who died from mesothelioma was evaluated for tissue burden of ferruginous bodies and uncoated asbestos fibers. The group contained individuals who had occupational exposure to asbestos and others had family members whose work history included vocations where contact with asbestos containing materials occurred. METHODS: Tissue samples from tumor free lung were digested and filtered and then investigated for ferruginous bodies by light microscopy and asbestos and non-asbestos fibers by analytical transmission electron microscopy (ATEM). Size and type of fibers were also analyzed. RESULTS: Asbestos bodies were found in 13 of the 15 samples and asbestos fibers were found in all cases. The most commonly found uncoated asbestos fiber in these individuals was amosite whereas tremolite was the second most commonly found form. The asbestos fiber burden in these females was often of mixed types. CONCLUSIONS: The asbestos body and fiber burden in these cases show variation in tissue burden. Some cases in this study had appreciable burden, which was attributed to secondhand exposure from occupationally exposed family members. Mesothelioma can occur also in individuals with comparatively low tissue burdens of asbestos.

Aged↗

PubMed1995

Asbestos causes DNA strand breaks in cultured pulmonary epithelial cells: role of iron-catalyzed free radicals.

Asbestos causes pulmonary fibrosis and various malignancies by mechanisms that remain uncertain. Reactive oxygen species in part cause asbestos toxicity. However, it is not known whether asbestos-induced free radical production causes alveolar epithelial cell (AEC) cytotoxicity by inducing DNA strand breaks (DNA-SB). We tested the hypothesis that asbestos-induced AEC injury in vitro is due to iron-catalyzed free radical generation, which in turn causes DNA-SB. We found that amosite asbestos damages cultured human pulmonary epithelial-like cells (WI-26 cells) as assessed by 51Cr release and that an iron chelator, phytic acid (500 microM), attenuates these effects. A role for iron causing these effects was supported by the observation that ferric chloride-treated phytic acid did not diminish WI-26 cell injury. Production of hydroxyl radical-like species (.OH) was assessed based upon the .OH-dependent formation of formaldehyde (HCHO) in the presence of dimethyl sulfoxide. A variety of mineral dusts induced significant levels of .OH formation (nmol HCHO at 30 min: carbonyl iron, 85 +/- 21; amosite asbestos, 14 +/- 2; chrysotile asbestos, 7 +/- 1; titanium dioxide, 2.5 +/- 0.5). Phytic acid significantly diminished the asbestos-induced .OH production. DNA damage to AEC was assessed by the alkaline unwinding, ethidium bromide fluorometric technique. Hydrogen peroxide caused dose-dependent DNA-SB in WI-26 cells after a 30-min exposure period [50% effective dose (ED50): 5 microM] that was similar to other cell lines. Amosite asbestos induced dose-dependent DNA-SB in WI-26, A549, and primary isolated rat alveolar type II cells maintained in culture for 7-10 days (alveolar type I-like). Lower doses of amosite (0.5-5 micrograms/ml or 0.25-2.5 micrograms/cm2) caused significant WI-26 cell DNA-SB after prolonged exposure periods (> or = 2 days). Phytic acid ameliorated DNA damage in all three cultured AEC. There was a direct correlation between mineral dust-induced .OH production at 30 min and DNA-SB in WI-26 cells at 4 h (P < 0.0005). These data suggest that mineral dusts can be directly genotoxic to relevant target cells of asbestos, AEC. Furthermore, these results provide additional support for the premise that iron-catalyzed free radicals mediate asbestos-induced pulmonary toxicity.

Asbestos↗

PubMed1993

Asbestos-related disease in the workplace and the environment: controversial issues.

Asbestos-related diseases continue to be sources of controversy for epidemiologist, clinician, and pathologist. Most investigators agree that the different fiber types behave differently in the lung, with chrysotile being rapidly removed, and amphibole persisting. These differences in biologic behavior probably account for the much greater disease potential of amphibole (amosite and crocidolite) compared with chrysotile asbestos, particularly in regard to mesothelioma induction in man. Asbestosis is defined as diffuse interstitial fibrosis of the lung caused by asbestos exposure, and this is the only condition to which the term asbestosis should be applied. The classical pathologic diagnostic criteria for asbestosis, namely the presence of diffuse interstitial fibrosis resembling usual interstitial pneumonia, and asbestos bodies visible in ordinary tissue sections, have proved to withstand the test of time. Cases without asbestos bodies visible in routine or iron-stained tissue sections almost never turn out to be asbestosis. It should be remembered that workers with asbestos exposure develop all of the interstitial lung diseases to which the remainder of the populace is subject; some of these conditions are treatable and should not be misdiagnosed as asbestosis, which is not treatable. There is strong epidemiologic and pathologic evidence that the only association of asbestos exposure and lung cancer is the association of asbestosis and lung cancer. Thus, a lung cancer should only be attributed to asbestos exposure when asbestosis is present on clinical or pathologic grounds. The histologic type and location of the tumor are irrelevant in this regard. Analytical electron microscopy indicates that chrysotile asbestos does induce mesothelioma in man, but that extremely high levels of retained fibers, levels as high as those seen in cases of asbestosis, are required for this event to occur. The weight of the evidence suggests that exposure of the general population to the very low levels of chrysotile that are found in some public building (levels not greatly different from ambient air) will never produce mesothelioma, asbestosis, or lung cancer because these diseases all appear to require quite high-level occupational chrysotile exposure. Even if one accepts the ideas (probably wrong) that any level of asbestos exposure carries a risk of cancer, and that mathematical extrapolation of risk from high-level occupational exposure to low-level building exposure is scientifically valid, the calculated risks are much smaller than real everyday risks such as driving to work. Thus, exposure to asbestos at environmental levels appears to produce no real dangers to health.

Asbestos↗

PubMed1990

[Respiratory malignancies induced by asbestos exposure and evaluation of cases with typical pleural malignant mesothelioma and lung cancer with asbestosis].

Asbestos exposure induces lung fibrosis, i.e. asbestosis, and furthermore, pathological changes of pleura, i.e. asbestos pleurisy of pleural plaque. Generally, asbestosis is induced by massive exposure to asbestos and pleural changes are induced by low dose exposure to asbestos. The most important diseases which are induced by asbestos exposure are malignancies, especially malignant mesothelioma and lung cancer. Two cases, one malignant mesothelioma, the other lung cancer with asbestosis induced by asbestos exposure received almost the same dose of asbestos, as estimated from the period of asbestos exposure and occupational history and the same kind of asbestos (crocidolite) and had a smoking history. We do not know which elements may induce malignancies under asbestos exposure. Recently, some reports described that asbestos mediated the transformation of genes and this action induced malignancies. We should extend our study to the gene problem in cases of malignant mesothelioma and lung cancer induced by asbestos exposure.

Aged↗

PubMed1982

Fiber counting and analysis in the diagnosis of asbestos-related disease.

Analysis of numbers and types of asbestos fibers present in lung tissue may provide insights into the pathogenesis of asbestos-induced disease, as well as diagnostic information concerning the relationship of a given lesion to asbestos exposure. This type of analysis requires extraction of fibers and asbestos bodies from lung tissue, preferably by means of a digestion-and-concentration technique, and examination with a combination of electron optical techniques, including electron diffraction and energy-dispersive x-ray spectroscopy. The combination permits definitive identification of asbestos fibers. Asbestos bodies have been shown to contain asbestos no matter what population they are found in, but they appear to be of value in ascertaining unusual exposure only when present in very large numbers. Numbers of asbestos bodies markedly underestimate total numbers of fibers present in lung. In patients from the general population, the mean number of asbestos fibers is about 1 X 10(6)/g dry lung; of this number, more than 80 per cent are fibers of chrysotile less than 5 microns long. Patients in the general population who have pleural plaques have about the same total number of fibers, but their lungs contain about a 50-fold increase in long thin amphibole fibers of commercial origin. Patients who have asbestosis and most patients who have mesothelioma have 100 to 200 X 10(6) fibers/g dry lung; the grade of asbestosis appears to be related to total fiber content. Occasional patients may develop mesotheliomas with much smaller fiber burdens. Both benign and malignant pleural diseases appear to be closely related to the presence of long thin amphibole fibers. Analysis of pulmonary fiber burden suggest that asbestos-related disease is not merely a matter of total numbers of fibers present, but that factors such as fiber type and size are equally important.

Asbestos↗

PubMed1996

Screening for asbestos-induced diseases in Finland.

Screening for asbestos-induced diseases in Finland was carried out in 1990-1992 as a part of the Asbestos Program of the Finnish Institute of Occupational Health. The aim of the present study was to find the workers who had developed an asbestos-induced disease in certain occupations. Examination of active or retired workers included a personal interview on work history and asbestos exposure, and a chest X-ray. The target group for the screening comprised workers under 70 years of age who had worked at least for 10 years in construction, 1 year in a shipyard or in the manufacture of asbestos products. A preliminary questionnaire was sent to 54,409 workers, 18,943 of whom finally participated in the screening examination. The mean age of the workers was 53 years; 95% were employed in construction, 2% in shipyards, and 3% in the asbestos industry. The criteria for a positive screening result were (1) a radiographic finding clearly indicating lung fibrosis (at least ILO category 1/1), (2) a radiographic finding indicating mild lung fibrosis (ILO category 1/0) with unilateral or bilateral pleural plaques, (3) marked abnormalities of the visceral pleura (marked adhesions with or without pleural thickening), or (4) bilateral pleural plaques. The positive cases totalled 4,133 (22%) and were sent for further investigation. In addition to the screening, information on the presence of asbestos in the work environment, prevention of asbestos exposure, as well as on the health effects of asbestos exposure and smoking were given to the participating workers. The screening acted as a preliminary survey to prompt further national follow-up of asbestos-induced diseases among the workers who have been exposed to asbestos. This article presents the material, methods, and overall results of the screening.

Adult↗

PubMedDate not supplied

Assessing asbestos exposure potential in nonindustrial settings.

The presence of asbestos containing materials (ACM) in office and commercial buildings is a significant environmental problem. Asbestosis, mesothelioma and lung cancer have been linked with industrial exposure to airborne asbestos. The extensive use of asbestos products in buildings has raised concerns about the widespread exposure of the general public to asbestos in nonoccupational settings. The presence of asbestos in a building does not necessarily mean that significant exposure of the occupants of the building has occurred, but it is important that the asbestos be monitored regularly to ensure that fibers do not become airborne. If ACM are contained within a matrix and not disturbed, exposure is unlikely. However, if the asbestos becomes friable (crumbling) or if building maintenance, repair, renovation or other activities disturb ACM, airborne asbestos fibers may be a source of exposure to the occupants of the building. Currently, asbestos exposure assessment is conducted by a phase contrast light microscope (PCM) technique. Due to its inherent limitation in resolution and the generic counting rules used, analysis by the PCM method underestimates the airborne asbestos fiber concentration as compared to analysis by transmission electron microscopy (TEM). It is important that the air monitoring results analyzed by PCM be interpreted carefully in conjunction with a survey by a professional to judge the physical condition of the ACM in buildings. Exposure levels to airborne asbestos fibers vary from day to day and depend on the physical condition of the material involved and the type of operating and maintenance program in place.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollution↗

PubMed2001

Changes in low molecular weight DNA fragmentation in white blood cells of workers highly exposed to asbestos.

OBJECTIVE: The aim of this study was to determine low molecular weight (LMW)-DNA fragmentation changes after white blood cell (WBC) incubation in lysis buffer followed by constant-field gel electrophoresis (CFGE). WBCs were isolated from blood samples of workers highly exposed to asbestos fibres at the workplace in Germany, and were compared with those from healthy adults. This study was conducted parallel to the study presented in our preceding paper (Marczynski et al. 2000b) in which we described significant increases in the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adducts in the DNA of white blood cells from the same highly exposed workers relative to the levels found in the control group in all three study years (1994 to 1997). METHOD: We found that 15-h incubation in lysis buffer of WBCs embedded in agarose-plugs from healthy control donors with 2% SDS, proteinase K and Na2-EDTA at 42 degrees C followed by 0.5 h at 4 degrees C produced a characteristic DNA fragmentation pattern below 23 kbp using CFGE. RESULTS: In the 1st year of the study (1994-1995) changes were found in LMW-DNA fragmentation in 54.8% of the asbestos workers studied, compared with the DNA fragmentation pattern of controls. Interestingly, in the 2nd year of the study (1995 1996) changes in DNA fragmentation were found in only 39.9% of exposed subjects. In the 3rd year of the study (1996-1997) the highest number of workers exposed to asbestos (67.3%) with changes in the LMW-DNA fragmentation pattern was found. The Chi-square test for each year of the study revealed significant changes (P < 0.001). These changes may be due to the presence of hydrogen peroxide (H2O2), as has been shown in vitro. It is likely that a Fenton reaction involving the heterolytic reduction of H2O2 by traces of reduced transition metals such as Fe2+ and Cu+ is involved in the fragmentation of DNA. No difference was found in the changes in DNA fragmentation between asbestos-exposed subjects with and without benign asbestos-associated diseases (asbestosis, asbestos-associated pleural plaques). Significant correlations were not found after analysis of the changes in DNA fragmentation in relation to different possible occupational and non-occupational confounding factors, such as the duration of asbestos exposure, the latency period, estimated cumulative fibrous dust dose ("fibre-years"), and non-occupational confounding factors, such as age, smoking status, acute febrile infections, the intake of medicines, aspirin, Ca2+, Mg2+ and/or hormones, the intake of vitamins, and cases of cancer. CONCLUSIONS: Our data confirm that oxidative stress occurs in the WBCs of workers highly exposed to asbestos fibres, thus supporting the hypothesis that asbestos fibres damage cells through an oxidative mechanism. Oxidative stress and oxidative DNA damage may be induced by long-term exposure to asbestos. The new insights into the oxidative effects of asbestos fibres are of great importance because they provide a way forward for new preventive strategies. Preventive and therapeutic approaches using antioxidants should be taken into consideration.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2004

Effects of asbestos on initiation of DNA damage, induction of DNA-strand breaks, P53-expression and apoptosis in primary, SV40-transformed and malignant human mesothelial cells.

Human mesothelial cells (HMC), the progenitor cells of asbestos-induced mesothelioma, are particularly sensitive to the genotoxic effects of asbestos, although the molecular mechanisms by which asbestos induces injury in HMC are not well known. The high susceptibility of HMC to simian virus 40 (SV40)-mediated transformation is assumed to play a causative role in the pathogenesis of mesothelioma. The aim of this study was to investigate the asbestos-induced DNA damage in cultured HMC and SV40-transformed HMC (MeT-5A) compared with their malignant counterparts, i.e. human mesothelioma cells (MSTO). The time-dependent initiation of DNA-strand breaks as well as the induction of oxidative DNA base modifications were key factors for investigation. HMC, MeT-5A and MSTO cells were exposed to chrysotile and crocidolite asbestos (3 microg/cm2) during different time periods (1-72 h). DNA damage was investigated by use of the Comet assay and alkaline unwinding, the latter in combination with the Fpg protein. The P53 level was analyzed by immunofluorescence, and measurement of apoptosis was conducted by flow cytometry. We found a significant induction of DNA damage in asbestos-treated HMC already after an exposure time of 1.5 h. This effect could not be observed in treated MeT-5A and MSTO cells. Also, a time-dependent significant increase in DNA-strand breaks was observed by alkaline unwinding in asbestos-treated HMC, but not in treated MeT-5A and MSTO cells. In none of the three cell lines we could detect oxidative DNA damage recognized by the Fpg protein (e.g. 8-oxo-guanine), up to 24 h after exposure to asbestos. In contrast to what was found in HMC, P53 was over-expressed in untreated MeT-5A and MSTO. The induction of apoptosis by asbestos fibers was suppressed in MeT-5A and MSTO cells. Crocidolite fibers induced the higher genotoxic effects and chrysotile the more pronounced apoptotic effects. We conclude that asbestos induces DNA damage in HMC already after a very short exposure time in the absence of 8-oxo-guanine formation. The presence of SV40-Tag in MeT-5A and MSTO cells results in an increased expression of P53, but not in additive genotoxic effects after exposure to asbestos. The deregulation of the apoptotic pathway may lead to proliferation of genomically damaged cells and finally to the development of mesothelioma.

Asbestos↗

PubMed1998

Cigarette smoke augments asbestos-induced alveolar epithelial cell injury: role of free radicals.

Cigarette smoke augments asbestos-induced bronchogenic carcinoma by mechanisms that are not established. Alveolar epithelial cell (AEC) injury due to oxidant-induced DNA damage and depletion of glutathione (GSH) and adenosine triphosphate (ATP) may be one important mechanism. We previously showed that amosite asbestos-induces hydroxyl radical production and DNA damage to cultured AEC and that phytic acid, an iron chelator, is protective. We hypothesized that whole cigarette smoke extracts (CSE) augment amosite asbestos-induced AEC injury by generating iron-induced free radicals that damage DNA and reduce cellular GSH and ATP levels. Asbestos or CSE each caused dose-dependent toxicity to AEC (WI-26 and rat alveolar type I-like cells) as assessed by 51chromium release. The combination of asbestos (5 microg/cm2) and CSE (0.O1-0.1%) caused synergistic injury whereas higher doses of each agent primarily had an additive toxic effect. Asbestos (5 microg/cm2) augmented CSE-induced (0.01-1.0%) AEC DNA damage over a 4 h exposure period as assessed by an alkaline unwinding, ethidium bromide fluorometric technique. These effects were synergistic in A549 cells and additive in WI-26 cells. Asbestos (5 microg/cm2) and CSE (0.5-1.0%) reduced A549 and WI-26 cell GSH levels as assessed spectrophotometrically and ATP levels as assessed by luciferin/luciferase chemiluminescence but a synergistic interaction was not detected. Phytic acid (500 microM) and catalase (100 microg/ml) each attenuated A549 cell DNA damage and depletion of ATP caused by asbestos and CSE. However, neither agent attenuated WI-26 cell DNA damage nor the reductions in GSH levels in WI-26 and A549 cells exposed to asbestos and CSE. We conclude that CSE enhance asbestos-induced DNA damage in cultured alveolar epithelial cells. These data provide additional support that asbestos and cigarette smoke are genotoxic to relevant target cells in the lung and that iron-induced free radicals may in part cause these effects.

Adenosine Triphosphate↗