Pulmonary fibrogenesis after three consecutive inhalation exposures to chrysotile asbestos

Our plain-English summary of Pulmonary fibrogenesis after three consecutive inhalation exposures to chrysotile asbestos, by P.G. Coin, A.R. Osornio-Vargas, V.L. Roggli, et al (American Journal of Respiratory and Critical Care Medicine, 1996).

The study

• Authors: P.G. Coin, A.R. Osornio-Vargas, V.L. Roggli, A.R. Brody
• Journal: American Journal of Respiratory and Critical Care Medicine
• Published: 1996;154(5):1511-9
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Previously, this laboratory developed a model of asbestos-induced pulmonary fibrogenesis in rats and mice after a brief (1 to 3-h) inhalation exposure. However, typical human environmental exposures would be repeated, although at lower concentrations than those used in our animal model. Here we have extended this model to encompass repeated exposures and consequent long-term effects. Groups of rats were exposed to chrysotile aerosol (10 mg/m3) for 3- to 5-h periods over 3 consecutive days. Lung fiber burden and pathologic features were studied for as long as 6 mo after exposure. We found that many of the longest (> or = 8 microm) fibers were retained in the lung for at least 6 mo, whereas shorter fibers were cleared more rapidly. The three exposures to chrysotile caused a large increase in DNA synthesis in the epithelium of terminal bronchioles and more proximal airways. When compared with a single exposure, the triple exposure caused an enhanced inflammatory response as well as a prolonged period of increased DNA synthesis in the proximal alveolar region. Hyperplastic, fibrotic lesions subsequently developed in the same region and persisted for at least 6 mo after exposure. These findings will be valuable in directing future studies of the mechanisms of pulmonary fibrosis in this model.

In plain English

This was an animal experiment from a laboratory that had earlier studied rats after a single brief inhalation exposure to chrysotile asbestos. Here, male Sprague-Dawley rats breathed chrysotile aerosol (10 mg/m3) for 3 to 5 hours on three consecutive days and were studied for up to 6 months. Comparison groups had one exposure, no exposure, or carbonyl iron dust. The longest fibers (8 micrometers or more) were cleared slowly. In the right apical lung lobe, an average of 4.2 million remained at day 1, 2.5 million at 30 days and 2.6 million at 180 days, while shorter fibers largely disappeared. Compared with one exposure, three exposures drew more macrophages to the first alveolar duct bifurcations. DNA synthesis, a sign of dividing cells, rose about 40-fold in terminal bronchioles and 15-fold at these bifurcations, and stayed raised at some sites for at least 14 days. Cell-rich, fibrotic lesions formed there and were still significantly enlarged at 180 days. Carbonyl iron caused no such lesions. The authors noted that their exposure levels were higher than typical human exposures.

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: Animal inhalation experiment (three separate experiments in rats), with single-exposure, sham/unexposed and carbonyl iron comparison groups
• Who was studied: Male specific pathogen-free Sprague-Dawley rats, 6 to 8 weeks old. Subgroups were two or more animals per time point (Experiment I), five to six (Experiment II) and four to six (Experiment III). The work was done at the National Institute of Environmental Health Sciences, North Carolina. Study dates were not given.
• Exposure: NIEHS intermediate chrysotile asbestos aerosol at 10 mg/m3 (respirable). Exposures were one or three 3-hour exposures (Experiment I), or three 5-hour exposures on consecutive days (Experiments II and III). Control animals had sham exposure, no exposure, or carbonyl iron aerosol at 50 mg/m3.
• Main results:
  • In triple-exposed rats, fibers 8 micrometers or longer averaged 4.2 million per right apical lobe at day 1, 2.5 million at day 30 and 2.6 million at day 180. Fibers 2 to 8 micrometers long fell from 45 million to 13 million to 2.3 million over the same times.
  • At 24 hours, triple-exposed rats had about twice as many macrophages per first alveolar duct bifurcation as single-exposed rats (mean 7.0 versus 3.9).
  • Triple chrysotile exposure raised neutrophils in pooled lung lavage to 9% at 1 day and 11% at 5 days, compared with less than 1% in cage controls. At 14 days the level was 3% in chrysotile-exposed rats and 2% in cage controls.
  • After three exposures, DNA synthesis (BrdU labeling) rose 40-fold in the terminal bronchiole and 15-fold at first alveolar duct bifurcations. It remained raised at some sites for at least 14 days after the last exposure. Carbonyl iron caused no increase.
  • Chrysotile caused an initial 40 to 50% increase in cross section at the first alveolar duct bifurcation, which fell to about 30% by 30 days. The increase was still statistically significant at 180 days.
  • Smaller increases of 10 to 15% at second bifurcations and alveolar duct septal tips were not statistically significant.
  • Cell counts (nuclear profiles) at the first alveolar duct bifurcation initially rose 60% in triple-exposed rats, falling to 30% at 14 days. Carbonyl iron caused no hyperplastic or fibrotic lesions.
• The authors' conclusion: The authors concluded that, compared with a single exposure, three brief chrysotile exposures produced more extensive and longer-lasting inflammatory and proliferative responses. They described the long-term persistence of lesions and fibers after relatively brief exposures as a novel finding that supports using their model to study how pulmonary fibrosis develops.
• Limitations the authors state:
  • The authors noted that typical human exposures are at lower concentrations than those used in this animal model.
  • Increased DNA synthesis in airways above the terminal bronchiole was not measured.
  • Macrophage concentrations seen at 30 and 180 days were not counted.
  • The exact identity of the labeled interstitial cells was not determined.

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Environmental Exposure, Fiber Burden, Epithelium, Pulmonary Fibrosis.

Related studies

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• Evaluation of the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study - Interim results Part 2: Histopathological examination, Confocal microscopy and collagen quantification of the lung and pleural cavity — D.M. Bernstein, B. Toth, et al. (2020)
• Dose-responsive increases in pulmonary fibrosis after inhalation of asbestos — T.R. Quinlan, J.P. Marsh, et al. (1994)
• Pulmonary toxicity of wollastonite in vivo and in vitro — E. Tátrai, Z. Kováciková, et al. (2004)
• Forsterite exposure causes less oxidative DNA damage and lung injury than chrysotile exposure in rats — A. Takata, H. Yamauchi, et al. (2009)

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