Asbestos: mechanisms of toxicity and carcinogenicity in the respiratory tract

Our plain-English summary of Asbestos: mechanisms of toxicity and carcinogenicity in the respiratory tract, by B. Mossman, W. Light, E. Wei (Annual Review of Pharmacology and Toxicology, 1983).

The study

• Authors: B. Mossman, W. Light, E. Wei
• Journal: Annual Review of Pharmacology and Toxicology
• Published: 1983;23:595-615
• Type of article: Review
• Cited by: 103 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 000634).

Summary of the article

This narrative review examined experimental work, mostly from the preceding decade, on how asbestos damages cells and causes cancer in the respiratory tract. The authors described the physical and chemical properties of chrysotile, said to make up about 95% of asbestos used worldwide, and of amphiboles such as crocidolite. They then summarized animal, organ-culture and cell-culture studies, including their own. In rats, mesothelioma after pleural injection was associated with fibers longer than 8 µm and thinner than 1.5 µm. Fiber surface charge correlated with red blood cell lysis (p < .01). In hamster tracheal cultures, Concanavalin A partially blocked chrysotile-induced mucin hypersecretion. Superoxide dismutase prevented the toxicity of long (>10 µm) but not short chrysotile, while catalase did not. Crocidolite led to squamous metaplasia, which retinyl methyl ether inhibited. When benzo(a)pyrene was coated on asbestos, about 70% entered tracheal cells within 1 hour and 50% remained at 8 hours. When the same amount was added directly to the medium, initial uptake was 20% and 5% remained at 8 hours. The authors concluded that asbestos damage begins at the plasma membrane and depends largely on fiber charge. They described asbestos as a complete carcinogen in mesothelial cells and fibroblasts, but said its role in bronchogenic carcinoma resembles that of a tumor promoter. They also raised concern about man-made and other natural fibers.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This 1983 article was a review, not a single new study. The authors reviewed experimental work, mostly from the preceding decade, on how asbestos damages cells of the respiratory tract. They also described their own laboratory experiments with chrysotile and crocidolite asbestos on red blood cells and on hamster tracheal tissue and cells. In these experiments, the surface charge of the fibers correlated with damage to red blood cells (p less than .01). At equal concentrations, long chrysotile fibers damaged tracheal cells more than short ones did. An enzyme called superoxide dismutase prevented the measured damage from long fibers but not the effects of short fibers. Crocidolite pushed the tracheal lining toward squamous metaplasia (an abnormal change in the lining), and a vitamin A analogue inhibited this change. When the carcinogen benzo(a)pyrene was coated on fibers, about 70% entered cells within 1 hour, compared with 20% when it was added directly to the culture medium. The authors concluded that asbestos acts as a complete carcinogen in mesothelial cells and fibroblasts. They concluded that in bronchogenic carcinoma its role resembles that of a tumor promoter. They noted that further confirmatory experiments were needed on whether asbestos alters DNA repair.

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 experimental studies on mechanisms of asbestos toxicity and carcinogenicity, including description of the authors' own laboratory (in vitro and organ culture) experiments
• Who was studied: Laboratory models rather than people: red blood cells, hamster tracheal organ cultures (N = 608 in the retinoid experiment), and cloned lines of hamster tracheal epithelial cells
• Exposure: Mainly UICC reference samples of Canadian chrysotile and Rhodesian crocidolite. Some experiments combined the fibers with polycyclic aromatic hydrocarbons (benzo(a)pyrene, 3-methylcholanthrene). Amosite and borosilicate glass were also mentioned in metaplasia work.
• Main results:
  • Fiber surface charge (zeta potential) correlated with the hemolytic activity of UICC chrysotile and crocidolite (p less than .01).
  • In tracheal explants, chrysotile-induced mucin hypersecretion was decreased by pre-addition of Concanavalin A (p less than .05).
  • In tracheal epithelial cell cultures, superoxide dismutase prevented the release of 75Selenium (a marker of membrane damage) and the decreased protein seen with long chrysotile fibers. It did not do so for short fibers. Catalase was not protective. The authors described longer fibers as more cytotoxic than shorter fibers at equal concentrations.
  • In organ cultures, crocidolite encouraged basal cell hyperplasia to progress to squamous metaplasia. The vitamin A analogue retinyl methyl ether inhibited asbestos-induced metaplasia and 3H-thymidine incorporation (p less than .01).
  • All minerals tested (crocidolite, hematite, kaolin, carbon) carried 3-methylcholanthrene into grafted tracheal explants (15 to 30 per group). With the hydrocarbon they were carcinogenic; without it they caused no tumors. At the highest dust amounts, crocidolite produced more malignancies than the other materials.
  • When benzo(a)pyrene was adsorbed to crocidolite or chrysotile, about 70% entered tracheal epithelial cells within 1 h and 50% remained at 8 h. When identical amounts were added directly to the medium, initial influx was 20% and 5% remained at 8 h.
  • DNA alkylation by benzo(a)pyrene was increased for as long as 5 days after it was introduced adsorbed to asbestos, which the authors said suggests impaired removal of DNA adducts.
• The authors' conclusion: The authors concluded that asbestos is a complete carcinogen in mesothelial cells and fibroblasts. They concluded that its role in bronchogenic carcinoma appears epigenetic, comparable to a classical tumor promoter acting after initiation by PAH or other chemical carcinogens.
• Limitations the authors state:
  • The authors stated that the findings on altered DNA repair require further confirmatory experiments.
  • The authors noted that long-term inhalation studies in rodents produce few malignancies, so comparative dose-response data for different fiber types are not available.
  • The authors noted that definitive epidemiologic data on man-made mineral fibers are unlikely before the year 2000.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Damages, Chrysotile, Amphibole Group, Crocidolite, Mesothelioma, Superoxide, Mesothelial Cells, Fibroblast.

Related studies

• In vitro approaches for determining mechanisms of toxicity and carcinogenicity by asbestos in the gastrointestinal and respiratory tracts — B.T. Mossman (1983)
• Solitary fibrous tumor of the upper respiratory tract. A report of six cases — G.B. Witkin, J. Rosai (1991)
• Host and environmental factors enhancing carcinogenesis in the respiratory tract — P. Nettesheim, D.C. Topping, et al. (1981)
• Systematic review and meta-analysis of epidemiological literature evaluating the association between exposure to man-made vitreous fibers and respiratory tract cancers — N. Suder Egnot, S.M. Benson, et al. (2020)
• A hypothesis concerning asbestos carcinogenicity: the migration of lipophilic carcinogens in adsorbed lipid bilayers — P. Gerde, P. Scholander (1987)
• Toxicity and carcinogenicity mechanisms of fibrous antigorite — V. Cardile, L. Lombardo, et al. (2007)

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