Effects of cigarette smoke and asbestos on airway, vascular and mesothelial cell proliferation

Our plain-English summary of Effects of cigarette smoke and asbestos on airway, vascular and mesothelial cell proliferation, by H. Sekhon, J. Wright, A. Churg (International Journal of Experimental Pathology, 1995).

The study

• Authors: H. Sekhon, J. Wright, A. Churg
• Journal: International Journal of Experimental Pathology
• Published: 1995;76(6):411-8
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

In order to determine whether exposure to both cigarette smoke and asbestos leads to enhanced cell proliferation, and whether pleura cell proliferation reflects the presence of fibres at or near the pleura, rats were exposed to air (control), daily cigarette smoke, a single intratracheal instillation of amosite asbestos, or a combination of smoke and asbestos. Dividing cells were labelled with bromodeoxyuridine (BrdU) and animals were sacrificed at 1, 2, 7 or 14 days. Both cigarette smoke and asbestos produced increases in the labelling index of small airway wall, epithelial cells and pulmonary artery cells. In the small airways there was a brief marked positive synergistic interaction between these two agents, but synergism was not seen in the vessels. Cigarette smoke did not increase the labelling of mesothelial or submesothelial cells, whereas asbestos caused a persisting increase in mesothelial cell labelling. There was no correlation between the number of BrdU labelled mesothelial or submesothelial cells and the number of fibres touching the pleura, or located within 180 microns of the pleura. We conclude that the combination of cigarette smoke and asbestos exposure produces a complex set of interactions and has the potential to markedly increase cell proliferation in the parenchyma, an effect that may be important in both fibrogenesis and carcinogenesis. In contrast to the diminishing effects over time of a single dose of asbestos on cell proliferation in the small airways and vessels, the same dose of asbestos leads to sustained mesothelial cell proliferation. However, the latter process does not correlate with local accumulation of asbestos fibres.

In plain English

This was an animal experiment in rats. The rats were split into four groups: air only (controls), daily cigarette smoke, a single dose of amosite asbestos placed into the windpipe, or both smoke and asbestos. Five or 6 rats per group were examined at 1, 2, 7 or 14 days, and dividing cells were counted in the small airways, nearby small arteries and the pleura (the lining around the lung). Both smoke and asbestos increased cell division in the small airways and arteries. In the airway lining, the combination produced a greater-than-additive increase at day 1 that had disappeared by day 2. No such effect was seen in the vessels. Except in one cell type at day 7, smoke did not increase division of pleural cells. Asbestos increased pleural cell division from day 2 onward, and this did not decrease over time. Pleural cell division did not correlate with the number of fibres touching or near the pleura. The authors cautioned that placing asbestos into the windpipe is a highly artificial method and that the results may not apply to all asbestos types.

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: rats exposed to air (control), daily cigarette smoke, a single intratracheal instillation of amosite asbestos, or both; dividing cells labelled with bromodeoxyuridine (BrdU) and counted
• Who was studied: Male Sprague-Dawley rats in four treatment groups; 5 or 6 animals per group were killed at each of four time points (1, 2, 7 or 14 days); conducted at the University of British Columbia, Vancouver, Canada (dates not stated)
• Exposure: UICC amosite asbestos, given once by intratracheal instillation at 2.5 mg in 0.5 ml saline; daily whole cigarette smoke (nose-only) in the smoke groups
• Main results:
  • Both cigarette smoke and asbestos increased the labelling index (share of dividing cells) in small airway walls, airway epithelial cells and pulmonary artery cells
  • In the airway epithelium of the combined smoke-plus-asbestos group, a synergistic (greater-than-additive) increase in labelling was present at day 1 and had disappeared by day 2
  • In the vessels there was no positive synergistic or additive interaction between smoke and asbestos; significantly negative (less-than-additive) interactions were found at a number of time points
  • In smoke-exposed rats, smoke did not increase labelling of mesothelial or submesothelial cells, except for submesothelial cells at day 7
  • In asbestos-exposed rats, labelling of both mesothelial and submesothelial cells increased significantly starting at day 2 and did not decrease over time
  • In the pleura, the combination of smoke and asbestos produced synergistic increases in labelling at day 1
  • There were no significant correlations between the number of BrdU-labelled pleural cells and the number of fibres in contact with, near, or distant from the pleura. Correlation coefficients were -0.02 for fibres in contact, -0.02 for fibres near and 0.07 for fibres distant
• The authors' conclusion: The authors concluded that combined cigarette smoke and asbestos exposure produces a complex set of interactions and can markedly increase cell proliferation in the lung tissue, which may be important in fibrogenesis and carcinogenesis. They also concluded that a single dose of asbestos leads to sustained mesothelial cell proliferation that does not correlate with local accumulation of fibres.
• Limitations the authors state:
  • Only amosite was used; whether the results apply to all types of asbestos is unclear, and chrysotile might behave differently
  • Intratracheal instillation is a highly artificial system and the results must be interpreted with great caution
  • The authors could not find non-parametric statistical tests suitable for examining interactions, because labelling indices were very low and often zero
  • The suggestion of a less-than-additive effect at later time points in the airways could not be proven statistically
  • The authors' comments on possible mechanisms were entirely speculative

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Pleura, Amosite, Asbestos Exposure, Parenchyma, Carcinogenesis.

Related studies

• Cigarette smoke increases the penetration of asbestos fibers into airway walls — D. McFadden, J. Wright, et al. (1986)
• Cigarette smoke makes airway and early parenchymal asbestos-induced lung disease worse in the guinea pig — V. Tron, J.L. Wright, et al. (1987)
• Retinoid signaling and activator protein-1 expression in ferrets given beta-carotene supplements and exposed to tobacco smoke — X.D. Wang, C. Liu, et al. (1999)
• Synergistic effects of mineral fibres and cigarette smoke on the production of tumour necrosis factor by alveolar macrophages of rats — Y. Morimoto, M. Kido, et al. (1993)
• Cigarette smoke, asbestos, and small irregular opacities — W. Weiss (1984)
• Cigarette smoke increases amosite asbestos fiber binding to the surface of tracheal epithelial cells — A. Churg, J. Sun, et al. (1998)

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