Evidence supporting a role for active oxygen species in asbestos-induced toxicity and lung disease

Our plain-English summary of Evidence supporting a role for active oxygen species in asbestos-induced toxicity and lung disease, by B.T. Mossman, J.P. Marsh (Environmental Health Perspectives, 1989).

The study

• Authors: B.T. Mossman, J.P. Marsh
• Journal: Environmental Health Perspectives
• Published: 1989;81:91-4
• Type of article: Review
• Cited by: 106 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos is an important occupational and environmental toxicant that affects several cell types in the respiratory tract. In an effort to understand how asbestos causes cell injury and/or altered proliferation and differentiation of cells, this laboratory has focused on reactive oxygen species as mediators of asbestos-induced biological effects. A compendium of experimental results reported by this laboratory and others supports this hypothesis. For example, scavengers of reactive oxygen metabolites and iron chelators (i.e., desferroxamine) prevent cytotoxicity after addition of asbestos to a variety of cell lines and macrophages in vitro. DNA strand breakage associated with toxicity of crocidolite asbestos in C3H10T 1/2 cells also is ameliorated with use of desferroxamine. All types of asbestos cause lipid peroxidation in mammalian cells and artificial membranes, a phenomenon that can be prevented by removal of catalytic iron. Last, asbestos causes generation of active oxygen species after interaction with leukocytes or by reduction of oxygen on the surface of the fibers.

In plain English

This article was a review, not a new study. The authors summarized laboratory experiments, from their own laboratory and others, on whether reactive (active) oxygen species help explain how asbestos damages cells. Most of the work was done on cells in culture, including tracheal epithelial cells, rat lung fibroblasts and macrophages. In the studies reviewed, antioxidants reduced cell death caused by crocidolite and long chrysotile fibers, and pretreating fibers with the iron-binding drug desferroxamine made crocidolite less toxic. One study of human mesothelial cells exposed to amosite found no protection from antioxidants. In another reviewed study, desferroxamine lessened DNA strand breaks caused by crocidolite. Asbestos fibers caused fat damage (lipid peroxidation) in red blood cells and cell membranes. In the authors' own earlier macrophage experiments, fibers caused more superoxide release than non-fibrous particles of similar chemistry. The authors concluded that the iron content of asbestos fibers is critical to producing these reactive oxygen species. They also stated that further experiments are needed to establish cause and effect between reactive oxygen and asbestos-related diseases.

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 laboratory (mostly in vitro) studies by the authors' laboratory and others
• Who was studied: No human subjects. The reviewed studies used cell lines and cells in culture: tracheal epithelial cells, rat lung fibroblasts, rodent alveolar and peritoneal macrophages, human mesothelial cells, red blood cells and C3H10T1/2 cells. Some used rat liver and lung microsomes, artificial membranes, and fibers alone without cells.
• Exposure: Asbestos fibers: crocidolite, chrysotile (including long fibers over 10 micrometers), amosite and anthophyllite. Comparison materials included other fibers (erionite, Code 100 fiberglass, sepiolite), non-fibrous particles (riebeckite, mordenite, glass) and titanium dioxide. Some experiments added antioxidants or the iron chelator desferroxamine.
• Main results:
  • In the authors' 1983 work, antioxidants (superoxide dismutase and dimethylthiourea) prevented death of tracheobronchial epithelial cells exposed to crocidolite and long chrysotile fibers.
  • In reviewed work, crocidolite was less toxic when the fibers were pretreated with the iron chelator desferroxamine.
  • A study by Gabrielson and colleagues found no reduction in cell damage when antioxidants were added to human mesothelial cells exposed to amosite. The authors suggested possible reasons for this negative result.
  • In a reviewed study (Turver and Brown), approaches using desferroxamine lessened DNA strand breaks caused by crocidolite in C3H10T1/2 cells, suggesting a role for iron.
  • In a 1975 study of red blood cells (Gabor and Anca), chrysotile caused the most lipid peroxidation at the same concentrations, followed by anthophyllite, amosite and crocidolite.
  • In the authors' laboratory's macrophage experiments, fibrous dusts (crocidolite, erionite, Code 100 fiberglass, sepiolite) significantly increased superoxide release from rat macrophages. Non-fibrous particles were less active than the matching fibers.
  • In studies done without cells, all types of asbestos catalyzed generation of hydroxyl radical, as shown by spin trapping.
• The authors' conclusion: The authors concluded that desferroxamine's inhibition of radical generation, cell death, lipid peroxidation and DNA breakage indicates that the iron content of asbestos fibers is critical to producing active oxygen species.
• Limitations the authors state:
  • The authors stated that further experiments are needed to establish a cause-and-effect relationship between active oxygen species and asbestos-associated diseases, including tests of antioxidants in animals.
  • The authors noted that production of oxygen metabolites by lung epithelial cells and fibroblasts exposed to asbestos had not been examined in detail.

Topics

Medical terms in this study, explained in our Lexicon: Reactive Oxygen Species (ROS), Macrophage, Crocidolite.

Related studies

• Implication of active oxygen species as second messengers of asbestos toxicity — B.T. Mossman, J.P. Marsh, et al. (1987)
• Scavengers of active oxygen species prevent cigarette smoke-induced asbestos fiber penetration in rat tracheal explants — A. Churg, J. Hobson, et al. (1989)
• Prevention of asbestos-induced cell death in rat lung fibroblasts and alveolar macrophages by scavengers of active oxygen species — M.A. Shatos, J.M. Doherty, et al. (1987)
• The role of free radicals in asbestos-induced diseases — D.W. Kamp, P. Graceffa, et al. (1992)
• Polyvinylpyridine-N-oxide and carboxymethyl cellulose inhibit mineral dust-induced production of reactive oxygen species by human macrophages — P. Nyberg (1991)
• Exercise alveolar-arterial oxygen pressure difference in interstitial lung disease — C. Risk, G.R. Epler, et al. (1984)

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