In vitro approaches for determining mechanisms of toxicity and carcinogenicity by asbestos in the gastrointestinal and respiratory tracts

Our plain-English summary of In vitro approaches for determining mechanisms of toxicity and carcinogenicity by asbestos in the gastrointestinal and respiratory tracts, by B.T. Mossman (Environmental Health Perspectives, 1983).

The study

• Author: B.T. Mossman
• Journal: Environmental Health Perspectives
• Published: 1983;53:155-61
• Type of article: Review
• Cited by: 56 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Organ and cell cultures of gastrointestinal and tracheobronchial epithelium have been used to document both the interaction of asbestos with mucosal cells and the sequence of cellular events occurring after exposure of cells to fibers. The biological activity of various types of asbestos in vitro is related to surface charge, crystallization, and dimensional characteristics. These factors also influence adsorption of natural secretions and serum components to fibers, a process that ameliorates cytotoxicity. Although mechanistic studies at the cellular level are lacking using epithelial cells of the digestive tract, asbestos appears to elicit a constellation of morphologic and biochemical changes in tracheal epithelium that resemble effects of classical tumor promoters on target cells.

In plain English

This 1983 article was a review, not a new study. The author discussed laboratory (in vitro) experiments, many from the author's own laboratory, in which asbestos was added to organ and cell cultures of gastrointestinal and respiratory lining cells, mostly hamster trachea and human bronchial tissue. The review reported that chrysotile was more toxic than the amphiboles amosite and crocidolite at equal concentrations. Toxicity depended on fiber surface charge, crystallization and size. In human bronchial cells, fibers longer than 10 micrometres were more toxic than fibers shorter than 2 micrometres. When the chemical carcinogen benzo(a)pyrene was attached to crocidolite or chrysotile, about 70% entered tracheal cells within 1 hour, compared with 20% when it was added directly to the culture medium. Amosite and crocidolite increased cell division in tracheal cells. Chrysotile and crocidolite raised the enzyme ornithine decarboxylase in a dose-dependent way. The author concluded that asbestos appeared to act epigenetically, like a classical tumor promoter. The author noted that this work used respiratory cells and that little experimental evidence existed for the gastrointestinal tract.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of in vitro (laboratory cell and organ culture) studies, including the author's own laboratory experiments
• Who was studied: No human or animal subjects. Organ and cell cultures of gastrointestinal and tracheobronchial epithelium (including hamster tracheal cultures and human bronchial explants), plus red blood cells in hemolysis tests reported from other researchers
• Exposure: Chrysotile, amosite and crocidolite asbestos added to cultures, in some experiments with benzo(a)pyrene (a polycyclic aromatic hydrocarbon) adsorbed to the fibers
• Main results:
  • Across the culture studies reviewed, chrysotile was more toxic than the amphiboles amosite and crocidolite when compared at equal concentrations
  • In experiments by Light and Wei cited in the review, under physiological conditions chrysotile carried a surface charge of +44.5 mV and crocidolite -43.5 mV. Chrysotile caused hemolysis of red blood cells, while crocidolite was only weakly hemolytic
  • In human bronchial epithelial cells, larger fibers (longer than 10 micrometres) were more cytotoxic than smaller fibers (shorter than 2 micrometres). The author's laboratory reported that damage to tracheal cells by longer fibers could be prevented by adding scavengers of oxygen-free radicals
  • When benzo(a)pyrene was adsorbed to crocidolite or chrysotile before it was added to tracheal epithelial cells, about 70% of it entered the cells within 1 hour, and 50% remained intracellular and unmetabolized at 8 hours
  • When the same amount of benzo(a)pyrene was added directly to the culture medium, only 20% entered the tracheal cells, and the cells retained 5% at 8 hours
  • After exposure to amosite or crocidolite, tracheal epithelial cells showed increased DNA synthesis (3H-thymidine uptake) and basal cell hyperplasia
  • Chrysotile or crocidolite increased ornithine decarboxylase in tracheal epithelial cells in a dosage-dependent fashion, though the size and timing of the response differed from that of the phorbol ester TPA
  • Studies cited in the review found that asbestos, unless combined with polycyclic aromatic hydrocarbons, was not carcinogenic in hamster tracheal implants, and was only weakly carcinogenic in rats after repeated intratracheal instillations
• The authors' conclusion: The author concluded that the role of asbestos in carcinogenesis appeared epigenetic, comparable to a classical tumor promoter rather than an initiator. The author also stated that there was little experimental evidence for this promoter-like activity in the gastrointestinal tract, and that mechanistic studies in esophagus, stomach and intestine cultures should be encouraged
• Limitations the authors state:
  • Only one research group had studied asbestos in gastrointestinal epithelial cells in vitro in depth
  • The author's own experiments used respiratory tract cells. Applying the results to the gastrointestinal tract rests on the cells being structurally and functionally similar

Topics

Medical terms in this study, explained in our Lexicon: Epithelium.

Related studies

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• Asbestos exposure and lymphomas of the gastrointestinal tract and oral cavity — R. Ross, R. Dworsky, et al. (1982)
• Cancer of the gastrointestinal tract and exposure to asbestos in drinking water among lighthouse keepers (Norway) — K. Kjaerheim, B. Ulvestad, et al. (2005)
• Aerodigestive and gastrointestinal tract cancers and exposure to crocidolite (blue asbestos): incidence and mortality among former crocidolite workers — A. Reid, G. Ambrosini, et al. (2004)

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