Inhaled asbestos fibers induce p53 expression in the rat lung

Our plain-English summary of Inhaled asbestos fibers induce p53 expression in the rat lung, by A. Mishra, J.Y. Liu, A.R. Brody, et al (American Journal of Respiratory Cell and Molecular Biology, 1997).

The study

• Authors: A. Mishra, J.Y. Liu, A.R. Brody, G.F. Morris
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1997;16(4):479-85
• Cited by: 36 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Humans and rodents exposed to an aerosol of asbestos fibers develop lung injury that can lead to a fibroproliferative response culminating in excessive scarring and impaired lung function. To define the early events that precede asbestos-induced fibrotic lung disease, rats were exposed to an aerosol of chrysotile asbestos fibers for 5 h. At various times after exposure, the lungs of the asbestos-exposed animals were evaluated immunohistochemically for expression of the p53 tumor suppressor protein, a growth regulatory protein. p53 became detectable by immunostaining at the predicted sites of fiber deposition (the bronchiolar-alveolar duct bifurcations) by 24 h after exposure. The number of cells positive for p53 immunostaining increased to a maximal level at 8 days after exposure, decreased by 14 days and returned to a low basal level at the 30-day time point. Control groups of rats that were unexposed or exposed to an aerosol of iron beads were negative for p53 immunostaining throughout the 30-day assessment period. Simultaneous detection of the proliferating cell nuclear antigen (PCNA) at the sites of fiber deposition in the asbestos-exposed animals agrees with our previous finding that p53 binds and regulates the PCNA promoter.

In plain English

In this animal experiment, male Sprague Dawley rats in three groups of 35 breathed, nose only, for 5 hours either chrysotile asbestos fibers (10 mg/m3), carbonyl iron spheres (50 mg/m3), or room air. Rats were killed immediately afterward or at 1, 2, 4, 8, 14 and 30 days. At each time point, lungs from 3 animals in each group were stained for two proteins: p53, a tumor suppressor protein, and PCNA, a protein involved in DNA copying and repair. In asbestos-exposed rats, p53 appeared by 24 hours where small airways branch into alveolar ducts, the main places fibers settle. The share of p53-positive cells there rose to 30 to 40% at 8 days, then waned, and expression disappeared by 1 month. Unexposed rats were negative for p53, and iron did not induce detectable p53. PCNA-positive cells peaked at about 50% at 4 days and stayed above control levels through 30 days. The authors concluded that inhaled asbestos induces p53 in the rat lung within 24 hours, suggesting a potential role for p53 in lung inflammation.

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: short-term inhalation exposure of rats followed by immunostaining of lung tissue at set time points, with iron-particle and air-exposed control groups
• Who was studied: Male Sprague Dawley rats, 8 to 10 weeks old, weighing 200 to 250 grams, in three groups of 35 rats each (Tulane University Medical Center, New Orleans). Five rats per group were killed immediately after exposure or at 1, 2, 4, 8, 14 and 30 days. At each time point, lung tissue from 3 animals in each group was examined.
• Exposure: A single 5-hour nose-only exposure to an aerosol of chrysotile asbestos fibers at 10 mg/m3. Control groups breathed carbonyl iron spheres at 50 mg/m3 or room air.
• Main results:
  • In asbestos-exposed rats, p53 became detectable at 24 hours after exposure in several cell types, including cells resembling macrophages, epithelial cells and interstitial cells.
  • In asbestos-exposed rats, the percentage of p53-positive cells at the bronchiolar-alveolar duct junctions rose to 30 to 40% at 8 days after exposure and waned thereafter.
  • In asbestos-exposed rats, p53 expression was transient and disappeared by 1 month after exposure.
  • Unexposed rats were negative for p53 staining throughout the lung.
  • Rats exposed to carbonyl iron particles showed no detectable p53 at any time after exposure.
  • In asbestos-exposed rats, PCNA-positive cells at the bronchiolar-alveolar duct junctions increased within 24 hours and reached a maximum of about 50% at 4 days. They remained higher than in the air and iron control groups through the 30-day time point.
  • Air-exposed and iron-exposed rats showed a variable low level of PCNA staining (under 10% of cells at the junctions) throughout the experiment.
  • PCNA messenger RNA was measured in one rat per group at 0 hours, 2 days and 2 weeks. It was higher in the asbestos-exposed rat at each time point.
• The authors' conclusion: The authors concluded that inhaled asbestos fibers induce p53 expression in the rat lung within 24 hours of exposure. They suggested this points to a potential role for p53 in lung inflammation.
• Limitations the authors state:
  • The authors did not quantify p53 staining in cells of the larger airways, although some were positive.
  • The authors stated that measuring the size of the change in PCNA messenger RNA would require more careful analysis.
  • The authors stated that the consequences of p53 expression in the lungs of asbestos-exposed animals remain to be determined.
  • The authors noted that the RNA probe was unexplainedly more prominent in the asbestos lanes. They suggested this may be due to probe sticking to residual asbestos in the samples.

Topics

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

Related studies

• Up-regulated expression of transforming growth factor-alpha in the bronchiolar-alveolar duct regions of asbestos-exposed rats — J.Y. Liu, G.F. Morris, et al. (1996)
• 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)
• Expression of genes coding for growth factors in experimental pneumoconiosis — G.F. Morris, J.Y. Liu, et al. (1996)
• p53, Cip1, and Gadd153 expression following treatment of A549 cells with natural and man-made vitreous fibers — N.F. Johnson, R.J. Jaramillo (1997)
• Aberrant expression of FoxP3 in a human T cell line possessing regulatory T cell‑like function and exposed continuously to asbestos fibers — M. Maeda, H. Matsuzaki, et al. (2018)
• Laser capture microdissection reveals dose-response of gene expression in situ consequent to asbestos exposure — Q. Yin, A.R. Brody, et al. (2007)

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