Implication of active oxygen species as second messengers of asbestos toxicity

Our plain-English summary of Implication of active oxygen species as second messengers of asbestos toxicity, by B.T. Mossman, J.P. Marsh, M.A. Shatos, et al (Drug and Chemical Toxicology, 1987).

The study

• Authors: B.T. Mossman, J.P. Marsh, M.A. Shatos, J. Doherty, R. Gilbert, S. Hill
• Journal: Drug and Chemical Toxicology
• Published: 1987;10(1-2):157-80
• Cited by: 37 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This chapter tested the hypothesis that cell damage by crocidolite and chrysotile asbestos involves the generation of active oxygen species. It summarized the authors' earlier work and reported new in vitro experiments with RL-82 rat lung fibroblasts. Earlier work had shown that superoxide dismutase and hydroxyl radical scavengers (mannitol, DMTU, sodium benzoate) inhibited crocidolite- and long chrysotile-associated 75Selenium release from hamster tracheal epithelial cells, while DABCO, a singlet oxygen scavenger, did not. In the first new experiment, UICC crocidolite was pretreated with 1, 5 and 10 mM of the iron chelators deferoxamine or Tiron, washed, and added to fibroblasts at 10 and 15 µg/cm2. Viability was assessed by trypan blue exclusion after 24 hours (N = 3 per group). Untreated crocidolite at these doses gave a decreased viability index of approximately 65% and 50%, respectively, compared with controls. Chelation significantly inhibited asbestos-associated cell death (p<.001) at all chelator concentrations. In the second experiment, a xanthine-xanthine oxidase superoxide-generating system was added at nontoxic concentrations. Xanthine alone had no effect, but xanthine plus xanthine oxidase (0.5 and 1.0 U/ml) increased both collagen and noncollagen protein synthesis at 48 and 72 hours. The authors concluded that asbestos damages cells primarily via reactive oxygen intermediates and that iron on the crocidolite fiber is a major factor in producing the hydroxyl radical.

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 1987 laboratory chapter summarized the authors' earlier work and reported new cell-culture experiments testing whether active oxygen species (oxygen free radicals) are involved in cell damage caused by asbestos. No people were studied; the work used rodent respiratory tract cells. In the new experiments, UICC crocidolite asbestos was first soaked in one of two iron-binding chemicals, deferoxamine or Tiron, and then added to rat lung fibroblast cells (RL-82). Untreated crocidolite at 10 and 15 ug/cm2 reduced the cells' viability. Fibers pretreated with either chemical caused significantly less cell death (p less than 0.001) at all chemical concentrations used. In a second experiment, a xanthine plus xanthine oxidase system that generates superoxide raised collagen and noncollagen protein production in the fibroblasts at 48 and 72 hours. Xanthine alone did not. The authors concluded that their studies suggest asbestos damages cells mainly by generating reactive oxygen intermediates, and that iron on crocidolite fibers is a major factor. They noted that the link to actual disease still had to be shown.

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: Laboratory (in vitro) cell-culture experiments, presented in a chapter that also summarizes the authors' earlier work
• Who was studied: Rodent respiratory tract cells and tissues: a hamster tracheal epithelial cell line, Fischer 344 rat lung fibroblasts, hamster tracheal explants and rat alveolar macrophages. The new chelator experiments used RL-82 rat lung fibroblasts, 3 dishes per group.
• Exposure: UICC crocidolite and Rhodesian and Canadian chrysotile, compared with nonfibrous analogs (riebeckite, antigorite), fiberglass, and long and short chrysotile. In the new experiments, crocidolite was pretreated with 1, 5 and 10 mM deferoxamine or Tiron. Separately, fibroblasts were exposed to a superoxide-generating xanthine-xanthine oxidase system (50 uM xanthine; 0.5 and 1.0 U/ml xanthine oxidase).
• Main results:
  • In RL-82 rat lung fibroblasts, untreated UICC crocidolite at 10 and 15 ug/cm2 caused a decreased viability index of approximately 65 and 50% respectively, compared with untreated control cells (as printed).
  • Crocidolite fibers pretreated with deferoxamine or Tiron caused significantly less cell death in the fibroblasts (p less than 0.001) at all chelator concentrations used.
  • In rat lung fibroblasts, xanthine alone did not change collagen or noncollagen protein production compared with untreated controls.
  • In rat lung fibroblasts, xanthine combined with xanthine oxidase (a superoxide-generating system) increased both collagen and noncollagen protein at 48 and 72 hours.
• The authors' conclusion: The authors concluded that their studies suggest asbestos damages cells primarily through generation of reactive oxygen intermediates. They added that the chelator results indicate iron on the crocidolite fiber is a major factor in producing the hydroxyl radical.
• Limitations the authors state:
  • The authors stated that a cause-and-effect relationship between free radical production by asbestos and the disease process had yet to be demonstrated; they were pursuing this in an animal model of asbestosis.
  • The authors noted a difference between the two exposures: asbestos increased the ratio of collagen to noncollagen protein, while the superoxide-generating system appeared to raise both in a similar fashion.

Topics

Medical terms in this study, explained in our Lexicon: Crocidolite, Chrysotile, Fibroblast, Superoxide, Hydroxyl Radical, UICC, Collagen, Damages.

Related studies

• Evidence supporting a role for active oxygen species in asbestos-induced toxicity and lung disease — B.T. Mossman, J.P. Marsh (1989)
• 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)
• Active oxygen species mediate asbestos fiber uptake by tracheal epithelial cells — J. Hobson, J.L. Wright, et al. (1990)
• Polyvinylpyridine-N-oxide and carboxymethyl cellulose inhibit mineral dust-induced production of reactive oxygen species by human macrophages — P. Nyberg (1991)
• Relationship of fiber surface iron and active oxygen species to expression of procollagen, PDGF-A, and TGF-beta(1) in tracheal explants exposed to amosite asbestos — J. Dai, A. Churg (2001)

Browse more research in Drug and Chemical Toxicology, or return to medical research.