Possible cellular and molecular mechanisms for asbestos carcinogenicity

Our plain-English summary of Possible cellular and molecular mechanisms for asbestos carcinogenicity, by C. Walker, J. Everitt, J.C. Barrett (American Journal of Industrial Medicine, 1992).

The study

• Authors: C. Walker, J. Everitt, J.C. Barrett
• Journal: American Journal of Industrial Medicine
• Published: 1992;21(2):253-73
• Type of article: Review
• Cited by: 89 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos fibers may exert their carcinogenic effects on mesothelial cells and bronchial epithelial cells by direct and indirect mechanisms. Direct effects can occur following the physical interaction of fibers with target cells or by the generation of free radicals from the fiber surface; indirect effects, following the interaction of fibers with inflammatory cells can result in the production of cellular mediators such as cytokines and various reactive oxygen species. As a result, target cells may be induced to proliferate and/or sustain genetic alterations, which lead to tumor development.

In plain English

This article was a review, not a new study. The authors summarized published laboratory, animal and human research on how asbestos fibers might cause mesothelioma and bronchogenic carcinoma. They described three routes: direct effects of fibers on target cells, free radicals generated at fiber surfaces, and indirect effects through inflammatory cells that release cytokines and reactive oxygen species. Among the earlier studies reviewed, long, thin fibers were much more likely than short, thick fibers to cause mesothelioma in rats. Asbestos did not cause gene mutations in test systems but did cause chromosome changes. In hamster cell experiments, milling fiberglass down to 2.2 micrometers cut its cell-transforming activity 10- to 20-fold. The authors also reviewed chromosome changes, growth-factor changes and limited oncogene data in mesothelioma cells. They noted that the combined effect of asbestos and smoking seen for bronchial cancer is not seen for mesothelioma. They noted that a direct role for any tumor suppressor gene in mesothelioma had yet to be demonstrated and that data on oncogenes were lacking. The authors concluded that multiple mechanisms, rather than a single one, were probably important in asbestos carcinogenicity.

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 published research on mechanisms of asbestos carcinogenicity (no new data collected)
• Who was studied: Earlier published studies covering cell cultures (rat and human mesothelial cells, Syrian hamster embryo cells, bronchial epithelial cells, macrophages), animal experiments, and chromosome studies of human and rodent mesotheliomas
• Exposure: Asbestos fibers in the reviewed studies, including chrysotile (Rhodesian chrysotile), crocidolite and amosite, plus other mineral fibers such as erionite and fiberglass; cigarette smoke as a co-exposure
• Main results:
  • Earlier rat studies by Stanton and colleagues, as reviewed, showed long (more than 4 micrometers), thin (less than 0.25 micrometer diameter) fibers were much more likely to cause mesothelioma than short, thick fibers. The authors said it was not clear whether the same applies to bronchogenic carcinoma.
  • Across the studies reviewed, asbestos did not act as a gene mutagen but caused chromosomal mutations (aneuploidy and aberrations) in many types of mammalian cells.
  • In a study by Lechner et al. cited in the review, human mesothelial cells were 10 times more sensitive than normal human bronchial epithelial cells, and 100 times more sensitive than fibroblastic cells, to the cell-killing effects of asbestos fibers. Mesothelial cells surviving two exposures to amosite showed chromosome losses.
  • In cited Syrian hamster embryo cell experiments (Hesterberg and Barrett), milling fiberglass to a length of 2.2 micrometers reduced transforming activity 10- to 20-fold. Further reduction to under 1 micrometer eliminated transforming activity at the doses tested.
  • In asbestos-transformed hamster cell lines (Oshimura et al.), an extra copy of chromosome 11 (trisomy 11) was the only chromosome change found in several of the lines.
  • The review cited a report of an excess of the short arm of chromosome 5 in 6 of 7 human mesothelioma cell lines (Pelin-Enlund et al.).
  • Cited studies found that normal human mesothelial cells do not produce the growth factor PDGF, while transformed mesothelioma cells appear to. In rats, spontaneous and fiber-induced mesothelioma cells did not express PDGF.
  • The authors noted, citing earlier studies, that the synergism between asbestos and cigarette smoking seen for bronchial cancers is not observed for mesotheliomas.
  • In one preliminary report cited (Barrett et al.), DNA from human mesothelioma cell lines tested positive in a mouse assay. The activated oncogene was not H-, K- or N-ras, and its identity remained to be determined.
• The authors' conclusion: The authors concluded that multiple mechanisms, rather than a single mechanism, are probably important in asbestos carcinogenicity, and that both mutagenic and epigenetic changes contribute to these cancers.
• Limitations the authors state:
  • The authors stated that a direct role for any tumor suppressor gene in the development of mesothelioma had yet to be demonstrated.
  • The authors stated that data on oncogene activation in mesothelioma were lacking and much more work was needed.

Topics

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

Medical terms in this study, explained in our Lexicon: Carcinogenic, Mesothelial Cells, Cytokine, Reactive Oxygen Species (ROS).

Related studies

• Cellular and molecular mechanisms of asbestos carcinogenicity: implications for biopersistence — J.C. Barrett (1994)
• Cellular and molecular mechanisms of asbestosis — B.T. Mossman, R. Gilbert, et al. (1986)
• A possible mechanism of chrysotile asbestos toxicity — G.L. Fisher, B.T. Mossman, et al. (1987)
• Cellular and molecular mechanisms of asbestos-induced fibrosis — R. Robledo, B. Mossman (1999)
• Molecular and Cellular Mechanism of Action of Chrysotile Asbestos in MRC5 Cell Line — A. Kussainova, O. Bulgakova, et al. (2023)
• Ascorbic acid modifies the surface of asbestos: possible implications in the molecular mechanisms of toxicity — G. Martra, M. Tomatis, et al. (2003)

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