Cellular ingestion, toxic effects, and lesions observed in human bronchial epithelial tissue and cells cultured with asbestos and glass fibers

Haugen, Aage; Schafer, Paul W.; Lechner, John F.; Stoner, Gary D.; Trump, Benjamin F.; Harris, Curtis C.

doi:10.1002/ijc.2910300303

Cited by 37 publications

(16 citation statements)

References 30 publications

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“…Chrysotile was the most cytotoxic fiber tested and even glass fibers were markedly toxic (chrysotile, 0.06; amosite, 0.10; crocidolite, 0.40; glass fibers, 1.02). Thus, the mesothelial cells were significantly more sensitive to asbestos and glass fibers than were previously tested normal human lung cells-i.e., the amosite 50o cytotoxic doses for bronchial epithelial and bronchial fibroblastic cells were 1.02 and 10.40 ,g of fibers per cm2 of culture dish surface area, respectively (18).…”

Section: Resultsmentioning

confidence: 95%

“…In fact, although exposure to chemicals and radiation has produced mesothelioma in experimental animals (1), no etiologic agent other than fibrous structures-i.e., zeolites, ceramics, and occasionally glasshas been identified as a causative agent for human pleural and peritoneal mesothelioma (1)(2)(3). Mesothelial cells actively ingest asbestos in a manner analogous to human bronchial epithelial cells (18), but the resultant effects are markedly more cytotoxic. This observation suggests that the mesothelial cell has unusual properties that increase its sensitivity to fibrous agents.…”

Section: Resultsmentioning

confidence: 99%

“…Electron Microscopy. Cultures were fixed and processed in situ for scanning electron microscopy by published procedures (18).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Asbestos-Associated Chromosomal Changes in Human Mesothelial Cells

Lechner

Tokiwa

Yeager

et al. 1985

In Vitro Effects of Mineral Dusts

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Replicative cultures of human pleural mesothelial cells were established from noncancerous adult donors. The cells exhibited normal mesothelial cell characteristics including keratin, hyaluronic acid mucin, and long branched microvilli, and they retained the normal human karyotype until senescence. The mesothelial cells were 10 and 100 times more sensitive to the cytotoxic effects of asbestos fibers than normal human bronchial epithelial or fibroblastic cells, respectively. In addition, cultures of mesothelial cells that survived two cytotoxic exposures of amosite fibers were aneuploid with consistent specific chromosomal losses indicative of clonal origin. These aneuploid cells exhibit both altered growth control properties and a population doubling potential of >50 divisions beyond the culture life span (30 doublings) of the control cells.Epidemiological studies have established that exposure to asbestos fibers is the primary cause of mesothelioma in the industrialized world (1-3). The latency period for this disease ranges from 15 to >40 years (4) and because of the high use of asbestos during and since World War II, the mortality rate from mesothelioma has doubled since 1967. Projections indicate that the incidence will continue to increase until the year 2007 (5). Carcinogenesis studies with animals have shown that mesothelioma can be caused by either intrapleural or intraperitoneal injections of asbestos (6, 7). In addition, phagocytosis of chrysotile asbestos by rat mesothelial cells in culture has been investigated (8). However, studies with human mesothelial cells have not been reported previously. In addition, the mechanisms by which asbestos causes mesothelioma remain obscure. Thus, we elected to investigate both short-and long-term effects of asbestos fibers on replicative cultures of normal human mesothelial cells. MATERIALS AND METHODSCell Culture and Growth Medium. Cultures of mesothelial cells were initiated from pleural effusions obtained from noncancerous donors who had medical indications of thoracentesis (e.g., congestive heart failure). The fluid was initially centrifuged at 125 x g for 5 min. The pelleted cells were suspended in growth medium, washed by centrifugation, resuspended in growth medium, and inoculated into surface-coated 10-cm culture dishes at a ratio of 1 dish per 50 ml of pleural fluid. Semiconfluent cultures were dissociated by using trypsin (9) and either expanded by inoculating 200,000 cells per 10-cm culture dish, cryopreserved (9), or used according to experimental protocols.Growth medium was prepared by supplementing medium M199 with hydrocortisone (0.4 ,AM), zinc-free insulin (0.87 ,uM), epidermal growth factor (3.3 nM), Hepes (20 mM), trace elements (9), fetal bovine serum (5%), and gentamicin (50 Ag/ml). Hydrocortisone was purchased from Steraloids (Wilton, NH); insulin and epidermal growth factor were obtained from Collaborative Research (Waltham, MA). Lux culture dish surfaces were coated (10) with a mixture of human fibronectin (10 pug/ml), collagen (Vitro...

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Asbestos-Associated Chromosomal Changes in Human Mesothelial Cells

Lechner

Tokiwa

Yeager

et al. 1985

In Vitro Effects of Mineral Dusts

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“…In this study the cell-associated fibers were assumed to be within phagosomes by virtue of the cells phagocytic activity and light microscopic appearance. In addition, fibers or particles have been detected in alveolar macrophages (10), type I epithelial cells (1,13,14), type II epithelial cells (1,15), tracheobronchial cells (16,17), and pleural mesothelial cells (18).…”

Section: Fa"00mentioning

confidence: 99%

Phagosomal pH and Glass Fiber Dissolution in Cultured Nasal Epithelial Cells and Alveolar Macrophages: A Preliminary Study

Johnson¹

1994

Environmental Health Perspectives

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The dissolution rate of glass fibers has been shown to be pH sensitive using in vitro lung fluid simulant models. The current study investigated whether there is a difference in phagosomal pH (ppH) between rat alveolar macrophages (AM) and rat nasal epithelial cells (RNEC) and whether such a difference would influence the dissolution of glass fibers. The ppH was measured in cultured AM and RNEC using flow cytometric, fluorescence-emission rationing techniques with fluorescein-labeled, amorphous silica particles. Glass fiber dissolution was determined in AM and RNEC cultured for 3 weeks with fast dissolving glass fibers (GF-A) or slow dissolving ones (GF-B). The mean diameters of GF-A were 2.7 pm and of GF-B, 2.6 pm, the average length of both fibers was approximately 22 to 25 pm. Dissolution was monitored by measuring the length and diameter of intracellular fibers and estimating the volume, assuming a cylindrical morphology. The ppH of AM was 5.2 to 5.8, and the ppH of RNEC was 7.0 to 7.5. The GF-A dissolved more slowly in RNEC than in AM, and no dissolution was evident in either cell type with GF-B. The volume loss with GF-A after a 3-week culture with AM was 66% compared to 45% for cultured RNEC. These results are different from those obtained using in vitro lung fluidsimulant models where dissolution is faster at higher pH. This difference suggests that dissolution rates of glass fibers in AM should not be applied to the dissolution of fibers in epithelial cells. -Environ Health Prospect 1 02(Suppl 5): 97-102 (1994)

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“…In vitro acellular systems have been developed to study the release of chemicals from fibers in conditions close to the physiological status (13)(14)(15)(16) (24) and an easy uptake have been reported (25,26). Fibers longer than the cell and extruding fibers often are noted with different cell types (19,(21)(22)(23). Ex vivo studies have confirmed that particle internalization occurs in vivo (27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

In Vitro Assessment of Biopersistence Using Mammalian Cell Systems

Jaurand¹

1994

Environmental Health Perspectives

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Biopersistence of fibers in the respiratory airways is a concept including both the physical durability of the fibers and their chemical stability. Physical durability results from several events of diverse origins: fiber epuration by the lung clearance mechanisms, internalization by scavenger cells and fiber splitting. Fibers residing in the lung milieu will be attacked and modified chemically, structurally, and physically (size and shape). Fiber toxicity, which is very likely to be dependent on physical fiber characteristics, will also be dependent on the duration of the fiber's stay in the tissue. Biopersistence, therefore, will be a key issue in determining fiber toxicity. So far, few in vitro systems have been used to study parameters involved in biopersistence. However, examples exist of investigations of fiber phagocytosis by mammalian cells in culture, either by macrophages, or epithelial or mesothelial cells, and studies have also been reported of the fate of internalized fibers in relation to fiber dimensions and chemical stability, especially within macrophages and mesothelial cells. The methods will be presented and discussed to determine to what extent the development of in vitro biophysical models could help in determining those parameters, known or thought to be relevant to fiber persistence. -Environ Health Perspect 102(Suppl 5): 55-59 (1994)

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Cellular ingestion, toxic effects, and lesions observed in human bronchial epithelial tissue and cells cultured with asbestos and glass fibers

Cited by 37 publications

References 30 publications

Asbestos-Associated Chromosomal Changes in Human Mesothelial Cells

Asbestos-Associated Chromosomal Changes in Human Mesothelial Cells

Phagosomal pH and Glass Fiber Dissolution in Cultured Nasal Epithelial Cells and Alveolar Macrophages: A Preliminary Study

In Vitro Assessment of Biopersistence Using Mammalian Cell Systems

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