Asbestos exposures: known and underrecognized sources.
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Biomedical subjects
Publications and source records attributed to R F Dodson.
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Digests of lungs, liver, and placenta from five stillborn infants of 22 to 38 weeks gestational age were examined for asbestos and other fibers using light and electron microscopy, energy dispersive X-ray analysis, and selected area diffraction analysis. Uncoated chrysotile asbestos fibers were found in the digests of at least one of the three tissues examined from each stillborn infant. The asbestos fiber burdens ranged from 71,000 to 357,000 fibers/g wet tissue. Most of the fibers were small, with the mean length ranging from 0.83 to 2.53 microns. While appreciable numbers of uncoated chrysotile fibers were present, no coated asbestos fibers were found in any of the stillborns. Both coated and uncoated nonasbestos fibers were found in at least one of the tissue digests of all five stillborns. The uncoated nonasbestos fibers were characterized as aluminum silicates, diatomaceous earth fragments, or other fibers. The coated nonasbestos fibers or ferruginous bodies were consistent with being formed on diatomaceous earth fragments, black carbon cores, or sheet silicate cores. Since the placenta is the only route of communication between the fetus and the outside environment, our findings strongly suggest a transplacental transfer of asbestos and other fibers in humans.
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Fiberoptic bronchoscopy has permitted the development of lavage procedures for the collection of lung washes. In certain disease states this material may contain large numbers of phagocytic cells (macrophages and neutrophils). Since these phagocytes are the predominant "dust scavenger cells" in the lung, the assessment of their particulate burden as well as that of the overall lavage material has been suggested as a potentially important diagnostic tool. The studies to date have shown that the presence of ferruginous bodies is an indication of past occupational exposure. In the present study, a digestion procedure was carried out on bronchoalveolar lavage material collected from individuals who were occupationally exposed to asbestos and from samples obtained from the general population. The parameters used for distinguishing the source of these samples included both light microscopy assessment of the filters for the presence of ferruginous bodies and electron microscopic screening for the presence of uncoated fibers.
An inherently long latency period exists between the time of asbestos exposure and the development of asbestos related clinical signs in man. By this stage the events reflect the cumulative responses and offer little with regard to characterizing the acute inflammatory reactions. Similarly, studies of asbestos-induced diseases employing animal models have often emphasized the investigation of chronic events, particularly the development of fibrosis and/or cancer. However, short-lived neutrophils, which exhibit a substantial potential to produce tissue damage through the generation of superoxide radicals and elastase, have been shown to constitute a component of the acute response to asbestos in this animal model. Repetitious exposures to asbestos could logically simulate extensions of this acute response and thus be an important contributor to the development of fibrosis. In order to assess this concept, animals received two exposures to asbestos. The parenchyma exhibited both 'established' lesions consisting primarily of foci of closely-packed, fibre-laden macrophages within alveoli, and 'new' lesions consisting of a mixed cell inflammatory response (including neutrophils and macrophages) as well as considerable alveolar exudate. Repeated infiltration of neutrophils to the site of renewed lung injury following a second exposure to asbestos may correspond to events occurring in human lungs exposed similarly to repeated exposures of the dust.
Autopsy samples from eight former shipyard workers were collected from lung parenchyma, tracheal lymph nodes, and pleural plaques. The tissue from each respective area was prepared by a modified bleach digestion technique, and the residue was collected on a 0.2-micron pore polycarbonate or 0.22-micron mixed cellulose ester filter. Quantitation of ferruginous bodies and uncoated fibers was done by light and transmission electron microscopy, respectively. Differences in the asbestos burden were noted for each site. Ferruginous bodies were observed in both parenchyma and nodes but not in plaques. Three subjects were found to have more ferruginous bodies per gram dry weight in their lymph nodes than in their lung parenchyma. Likewise, all subjects were found to have more uncoated fibers per gram in the nodes than in the parenchyma. Amphibole and chrysotile fibers were noted in the lung and extrapulmonary sites, with chrysotile being the predominant asbestiform in plaques. The majority of the uncoated fibers in both the nodes and the plaques were less than or equal to 5 microns in length. However, some fibers with dimensions conforming to the "Stanton hypothesis" reached both areas. These residual patterns most likely reflect the impact of clearance on lung burden as opposed to the eventual accumulation and stasis in the extrapulmonary areas.
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The relationship of free arachidonic acid (AA) to cellular permeability, lipid peroxidation and physical state "fluidity" of the membrane was investigated in cultured endothelial cells (EC) dissociated from cerebral microvessels of rats. The results demonstrate that AA can induce a reversible alteration of endothelial permeability to trypan blue albumin (TBA). Exposure of EC to AA increases membrane "fluidity" as measured by fluorescence anisotropy using 1,6-diphenyl-1,3,5 hexatriene as a fluorescent probe. The AA modification of EC membrane "fluidity" is not associated with changes in EC permeability. Addition of AA and H2O2 to the incubation medium of EC leads to persistant alteration of EC permeability which can be prevented by catalase treatment. Both AA and H2O2 induce a greater formation of malondialdehyde, the product of lipid peroxidation, than AA alone. These findings strongly suggest that a release of AA either from the capillary or cellular membrane of the brain under a pathological condition may alone or through a peroxidative process alter the function of blood-brain barrier.
We used analytical electron microscopic techniques, including energy-dispersive X-ray analysis, to evaluate a patient with diffuse infiltrates and a history of silica exposure. We identified silica particles in digested bronchoalveolar lavage fluid, sectioned alveolar macrophages recovered by lavage, and parenchymal specimens obtained by transbronchial biopsy. This analysis confirmed our clinical suspicion (a sporadic case of accelerated silicosis) and eliminated the need for additional, more complicated, diagnostic procedures.
Ferruginous bodies (FB) in sputa are recognized as an indicator of past exposure to asbestos. However, a great variability exists in FB production, even in individuals with a history of occupational exposure. A further complication in interpreting the presence of FBs in sputa is that all individuals in modern society are exposed to asbestos and, in lung tissue studies, have been shown to harbor appreciable numbers of asbestos fibers. Thus, some of these individuals should occasionally produce FBs in their sputa. The present study was undertaken to determine if uncoated asbestos fiber content could be used to better discriminate occupationally exposed individuals from the general population. Randomly selected sputum samples from 12 former workers in an amosite asbestos plant and 12 controls were studied. The samples were prepared for the study by digesting the sputa in sodium hypochlorite. The digests were filtered through 0.2-microns polycarbonate filters for collection of particulates. The filters were screened for FBs by light microscopy at 200 X, and the presence or absence of uncoated asbestos fibers was determined at 5000 X in an AMRAY 1000A scanning electron microscope. The use of electron microscopy revealed the presence of commercial amphiboles in the sputa of the occupationally exposed individuals and enabled a differentiation of these samples from those of the general population.
The effects of respirable environmental fibers on cultures of human umbilical vein and bovine pulmonary artery endothelial cell monolayers were studied. Interaction among endothelial cell monolayers and amosite and chrysotile asbestos, attapulgite, fiberglass, or latex beads resulted in rapid phagocytosis of the particulates. A gradient of time-dependent and concentration-dependent endothelial cell injury (measured by specific 51Cr release) was observed with amosite and attapulgite being markedly toxic. Chrysotile and fiberglass were much less toxic, and latex beads were not significantly injurious at any time or dose examined. Responses of bovine pulmonary artery and human endothelial vein endothelial cells to fiber phagocytosis and fiber-induced injury were similar. In human umbilical cell monolayers, fiber-mediated stimulation of the arachidonate metabolite prostacyclin paralleled endothelial cell injury; i.e. amosite and attapulgite were stimulatory, whereas fiberglass (0-500 micrograms/ml) and latex beads (10(9) beads/ml) did not significantly increase prostacyclin generation. Although chrysotile was only weakly cytotoxic, significant stimulation of prostacyclin was observed at the highest dose tested (500 micrograms/ml). To investigate whether toxic oxygen species may be involved in fiber-induced cytotoxicity, oxidant scavengers or inhibitors were used in injury studies. Both superoxide dismutase (a scavenger of O2-) and catalase (an inhibitor of H2O2) produced significant protection against fiber-mediated endothelial cell injury. In addition, chelation by deferoxamine of elemental Fe present in the fiber preparations was also protective, suggesting Fe, via the modified Haber-Weiss reaction, may promote hydroxyl radical formation and contribute to endothelial cell injury induced by these particulates. These results suggest that the interaction within the interstitial environment between endothelial cells and occupationally relevant dusts may be important in fiber-mediated inflammatory processes in the lung.
Vascular endothelial cell injury is important in the development of a variety of chronic interstitial lung disorders. However, the involvement of such injury in the inflammatory response associated with the inhalation of asbestos fibers is unclear and the mechanism of asbestos fiber cytotoxicity remains unknown. In the present study, human umbilical vein endothelial cells were challenged with amosite asbestos and several parameters of cellular function were examined. Electron microscopic examination revealed that endothelial cell exposure to asbestos resulted in active phagocytosis of these particulates. Biochemical evidence of dose-dependent asbestos-mediated endothelial cell activation was indicated by increased metabolism of arachidonic acid. For example, amosite asbestos (500 micrograms/ml) produced a ninefold increase in prostacyclin (PGI2) levels over those levels in non-exposed cells. Incubation of human endothelial cells with asbestos fibers induced specific 51Cr release in both a dose- and time-dependent fashion indicative of cellular injury. Injury induced by amosite asbestos was not significantly attenuated by treatment of the endothelial cell monolayer with either the iron chelator deferoxamine, which prevents hydroxyl radical (.OH) formation, or by the superoxide anion (O2-) scavenger, superoxide dismutase. However, significant dose-dependent protection was observed with the hydrogen peroxide (H2O2) scavenger, catalase. Chelation of elemental iron present within amosite asbestos fibers by deferoxamine produced a 33% reduction in asbestos cytotoxicity, suggesting a potential role for hydroxyl radical-mediated injury via the iron-catalyzed Haber-Weiss reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
Since asbestos burden in the lung can very among areas, the usefulness of small tissue samples for identifying past occupational exposure is examined. Simulated transbronchial biopsy samples and open lung biopsy samples were collected from autopsy material from 12 former amosite asbestos workers and ten persons from the general population. Tissue evaluation included (1) paraffin embedment and light microscopy screening for fibrosis and ferruginous bodies, and (2) tissue digestion, which was analyzed by the combination of (A) light microscopy screening for ferruginous bodies and (B) electron microscopy (EM) screening for uncoated fibers. Using standard pathology techniques to classify the small samples was generally unsuccessful, the samples being too small or their size compounding other random sampling problems. The most reliable method of establishing which transbronchial biopsy tissue samples were from the occupationally exposed group occurred when light and EM analyses were used to evaluate digested tissue. The combined data from the EM analysis of two samples per subject indicated controls had two or fewer observed asbestos fibers, while the amosite asbestos workers had six or more fibers. This distinction was valid even in those who, 21 years before sampling, had worked for only a few weeks in the asbestos plant.
Asbestos is a recognized carcinogen which is widely available for environmental exposure. Since all members of our society are exposed to asbestos containing environments and, indeed, have asbestos fibres in their lungs, the concern exists as to its significance in contributing to the incidence of lung cancer in such populations. The asbestos burden was compared in lung tissue from control and lung cancer patients who had resided in a non-urban environment. There were no significant differences between the asbestos burdens in both age matched groups; however, the proportions of amphiboles to chrysotile were different from those reported in previous urban based studies. This difference was suggested to be attributable to chrysotile exposure in urban air. All patients had appreciable non-asbestos fibres within their lungs. The results indicate that when comparing any dust burden in lungs, it is necessary to have data from regional control populations before attempting to explore causal-disease relationships.
A direct method for measuring mean linear intercepts (Lm) was tested. A semi-automatic image analysis system (Zeiss, Videoplan) and an overlay of parallel lines were employed in determining Lm in intravascularly perfused guinea pig lungs. Actual chord lengths were recorded and the data was immediately processed. Spurious intercepts and manual data manipulation were avoided. This direct method of measurement proved to be simple, rapid and very consistent across three trials for each animal. Analysis of variance revealed no significant differences between the three trials (p = 0.22).