Diseases caused by asbestos: mechanisms of injury and disease development

Our plain-English summary of Diseases caused by asbestos: mechanisms of injury and disease development, by C.B. Manning, V. Vallyathan, B.T. Mossman (International Immunopharmacology, 2002).

The study

• Authors: C.B. Manning, V. Vallyathan, B.T. Mossman
• Journal: International Immunopharmacology
• Published: 2002;2(2-3):191-200
• Type of article: Review
• Cited by: 171 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos is a ubiquitous, naturally occurring fiber that has been linked to the development of malignant and fibrotic diseases of the lung and pleura. These diseases may be initiated by injury to epithelial cells and mesothelial cells by asbestos fibers through the formation of reactive oxygen intermediates. Elaboration of oxidants are also a consequence of inflammation, a hallmark of exposure to asbestos after inhalation or injection of asbestos fibers into animals. The type, size, and durability of asbestos fibers may be important in toxicity and pathogenicity of asbestos types. This review discusses the pathways of oxidant generation by asbestos fibers, cell-cell interaction that may initiate and perpetuate inflammation, cytokine release and proliferative responses to asbestos, and cell signaling pathways implicated in these events.

In plain English

This article was a review, not a new study. The authors, from the University of Vermont and the National Institute for Occupational Safety and Health, summarized published epidemiologic, animal and cell studies, including work from their own laboratories, on how asbestos injures the lung and pleura. They briefly described asbestosis, pleural plaques, lung cancer and mesothelioma. The review stated that amphiboles such as amosite, crocidolite and tremolite have the greatest potential, and chrysotile the least, to cause mesothelioma. It added that chrysotile's role is debated because lung fiber analysis suggests tremolite in the ore may be the actual cause. It described evidence that fibers with more iron, and longer fibers, generate more reactive oxygen species. It also described laboratory and animal work showing that asbestos activates inflammatory signals such as TNF and the gene-control proteins AP-1 and nuclear factor-kappa B. In transgenic mice, AP-1 activation rose 10-fold in lung tissue and 22-fold in bronchial tissue. The authors concluded that asbestos activates multiple signaling pathways through oxidant-dependent routes, and that the precise mechanisms remain open for investigation.

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: Narrative review of published research on mechanisms of asbestos-related disease, including the authors' own laboratory work; no new data were collected
• Who was studied: No new population was studied. The review drew on published epidemiologic studies of asbestos-exposed workers, animal studies (rats and mice, including transgenic mice) and cell-culture studies (for example rodent tracheal epithelial and mesothelial cells).
• Exposure: Asbestos in general: chrysotile (serpentine) and the amphiboles amosite, crocidolite, tremolite, actinolite and anthophyllite. Crocidolite and chrysotile were the main fibers in the laboratory and inhalation studies discussed. Erionite and silica were also mentioned.
• Main results:
  • The review stated that commercial amphiboles (amosite, crocidolite, tremolite) have the greatest potential and chrysotile the least potential to induce mesothelioma.
  • The review stated that chrysotile's potential to cause mesothelioma is debated, citing lung fiber analysis evidence suggesting that tremolite, a component of the ore, is the actual cause.
  • The review stated that asbestos-induced mesothelioma usually has a latency of 30 or more years.
  • The review stated that mesothelioma is not associated with cigarette smoking.
  • The review stated that cigarette smoking and asbestos exposure have additive or synergistic interactions in causing lung cancer.
  • Citing earlier studies, the review stated that radiographic asbestosis is not a prerequisite for the increased lung cancer risk associated with asbestos.
  • The review stated there is no consistent reliable evidence linking asbestos exposure to a specific lung cancer cell type or to a specific site or lobe of tumor origin.
  • The review reported that asbestos fibers with more iron, and longer fibers, have been shown to generate more reactive oxygen species (ROS).
  • In a cited mouse study, knockout mice lacking the TNF receptor made more TNF when exposed to chrysotile but did not develop the fibrotic lesions seen in normal (wild-type) mice.
  • The authors' laboratories found that asbestos and erionite increased mRNA levels of the early response proto-oncogenes c-fos and c-jun in rodent tracheal epithelial and mesothelial cells. Nonpathogenic fibers and particles did not have this effect.
  • In cited rat inhalation studies comparing crocidolite and chrysotile, increased c-jun was found in lung tissue of crocidolite-exposed rats, which later developed pulmonary fibrosis.
  • In NIOSH studies of transgenic mice exposed to crocidolite, AP-1 activation increased 10-fold in lung tissue and 22-fold in bronchial tissue.
  • The authors' laboratories found that crocidolite caused protracted and dose-related increases in NF-kappa B DNA binding in tracheal epithelial cells.
• The authors' conclusion: The authors concluded that studies in their laboratories show multiple signaling pathways and transcription factors are activated by asbestos fibers through oxidant-dependent pathways, driven mainly by iron-related reactions on the fiber surface. They presented this as a hypothetical scheme.
• Limitations the authors state:
  • The authors stated that the precise changes asbestos causes in signaling molecules are not yet known and remain to be investigated.
  • The authors described their overall scheme linking signaling events to asbestos-related disease as hypothetical.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleura, Mesothelial Cells, Inflammation, Cytokine.

Related studies

• Exposure science will not increase protection of workers from asbestos-caused diseases: NIOSH fails to provide needed public health action and leadership — R.A. Lemen, H. Anderson, et al. (2011)
• Multiple mechanisms for the carcinogenic effects of asbestos and other mineral fibers — J.C. Barrett, P.W. Lamb, et al. (1989)
• Protective effect of natural flavonoids on rat peritoneal macrophages injury caused by asbestos fibers — V.A. Kostyuk, A.I. Potapovich, et al. (1996)
• The function, mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: a review focused on the genes' molecular mechanisms — L.V. de Assis, M.C. Isoldi (2014)
• Asbestos: when the dust settles an imaging review of asbestos-related disease — H.D. Roach, G.J. Davies, et al. (2002)
• Malignant pleural mesothelioma caused by environmental exposure to asbestos in the Southeast of Turkey: CT findings in 117 patients — A. Senyiğit, H. Bayram, et al. (2000)

Browse return to medical research.