Chrysotile asbestos inhalation induces tritiated thymidine incorporation by epithelial cells of distal bronchioles

Our plain-English summary of Chrysotile asbestos inhalation induces tritiated thymidine incorporation by epithelial cells of distal bronchioles, by P.D. McGavran, A.R. Brody (American Journal of Respiratory Cell and Molecular Biology, 1989).

The study

• Authors: P.D. McGavran, A.R. Brody
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1989;1(3):231-5
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Previous studies in a rat model of asbestosis have demonstrated increased incorporation of tritiated thymidine by bronchiolar and alveolar epithelial cells 19 to 72 h after a single, 5-h exposure to chrysotile asbestos. This increase in thymidine labeling occurred at the first alveolar duct bifurcations, where terminal bronchioles end and where asbestos deposition is most concentrated. To determine whether airways more proximal than the terminal bronchioles exhibit a similar type of proliferative response to asbestos, incorporation of tritiated thymidine by airway epithelial cells was determined by light microscopic autoradiography. Incorporation by the epithelium in regions of the trachea, mainstem bronchi, and bronchioles was measured in lung tissue from sham-exposed and chrysotile asbestos-exposed rats, zero and 33 h after exposure. Sham-exposed animals and those studied immediately after exposure exhibited no increases in tritiated thymidine incorporation at any airway level. Tritiated thymidine incorporation by epithelial cells of bronchioles in peripheral regions of the lungs was significantly increased, as much as 20-fold, 33 h after chrysotile exposure. In the same asbestos-exposed animals, epithelial cells of the trachea, the bronchi, and the larger bronchioles did not exhibit increased cell labeling. The fact that asbestos was deposited throughout all airway levels, yet increased thymidine incorporation is observed primarily in the peripheral bronchiolar regions, raises interesting questions regarding the mechanisms of asbestos-induced cell proliferation.

In plain English

This was an animal experiment in male rats. The authors exposed rats for 5 hours to an aerosol of chrysotile asbestos (10 mg per cubic meter, respirable mass) and compared them with sham-exposed rats. Zero or 33 hours after exposure, the rats received tritiated thymidine. The authors then counted the percentage of lining (epithelial) cells in the trachea, bronchi and smaller airways that had taken it up, as a measure of cell proliferation. In sham-exposed rats, labeling was less than 1% at all airway levels, and rats examined immediately after exposure showed no increase. At 33 hours, labeling was not significantly increased in the trachea, bronchi and large airways within 8 mm of the carina, but it was significantly increased in airways farther out. In the most distal region (12 to 16 mm), which included terminal bronchioles, the mean labeling index was 5.4%, approximately a 10-fold increase. Most of the labeled bronchiolar cells could be identified as nonciliated Clara cells. The authors concluded that the peripheral bronchioles showed the greatest increases. They said their findings were consistent with the idea that macrophages may mediate this response, but this remains to be determined.

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 experiment (inhalation exposure in rats, with sham-exposed controls, measured by light microscopic autoradiography)
• Who was studied: Male CD (SD)BR rats, 8 weeks old; sham-exposed rats and asbestos-exposed rats examined 0 and 33 hours after exposure. The number of rats per group and airway level, as printed in the figure, ranged from 2 to 6.
• Exposure: A single 5-hour exposure to an aerosol of chrysotile asbestos at 10 mg per cubic meter (respirable mass)
• Main results:
  • In sham-exposed rats, labeling of airway epithelial cells was less than 1% at all levels of the lung
  • Rats examined immediately (0 hours) after asbestos exposure showed no increase in labeling in any airway
  • In asbestos-exposed rats, labeling in the trachea, bronchi and large airways within 8 mm of the carina was not significantly increased at either time point
  • At 33 hours after exposure, labeling of epithelial cells was significantly increased in airways more than 8 mm beyond the carina
  • At 33 hours after exposure, epithelial cells in the lower lung regions (12 to 16 mm below the carina, including terminal bronchioles) had a mean labeling index of 5.4%, approximately a 10-fold increase in the labeling index
  • The trend toward increasing labeling as airways became smaller was statistically significant (p less than 0.001) at 33 hours
  • The majority of labeled bronchiolar cells could be identified as nonciliated Clara cells, by their granule content and dome-shaped apices
• The authors' conclusion: The authors concluded that the epithelium of the peripheral bronchioles showed the greatest increases in tritiated thymidine incorporation. They said the pattern was consistent with the hypothesis that the proliferative response may be mediated by activated alveolar and/or interstitial macrophages, which they said had yet to be determined.
• Limitations the authors state:
  • The authors stated that the 5.4% mean for the lower lung is probably an underestimate because it includes data from larger bronchioles along with the ends of terminal bronchioles

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Deposition, Epithelium, Bronchus.

Related studies

• Incorporation of tritiated thymidine by epithelial and interstitial cells in bronchiolar-alveolar regions of asbestos-exposed rats — A.R. Brody, L.H. Overby (1989)
• Asbestos and benzo[a]pyrene act synergistically to induce squamous metaplasia and incorporation of [3H]thymidine in hamster tracheal epithelium — B.T. Mossman, A. Eastman, et al. (1984)
• Multi-walled carbon nanotubes directly induce epithelial-mesenchymal transition in human bronchial epithelial cells via the TGF-β-mediated Akt/GSK-3β/SNAIL-1 signalling pathway — M. Polimeni, G.R. Gulino, et al. (2016)
• Asbestos induces tissue factor in Beas-2B human lung bronchial epithelial cells in vitro — A. Iakhiaev, U. Pendurthi, et al. (2004)
• Thymidine incorporation by lung fibroblasts as a sensitive assay for biological activity of asbestos — I. Lemaire, D. Gingras, et al. (1982)
• Ozone enhances the uptake of mineral particles by tracheobronchial epithelial cells in organ culture — A. Churg, M. Brauer, et al. (1996)

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