Comparative proliferative and histopathologic changes in rat lungs after inhalation of chrysotile or crocidolite asbestos

Our plain-English summary of Comparative proliferative and histopathologic changes in rat lungs after inhalation of chrysotile or crocidolite asbestos, by K.A. BéruBé, T.R. Quinlan, G. Moulton, et al (Toxicology and Applied Pharmacology, 1996).

The study

• Authors: K.A. BéruBé, T.R. Quinlan, G. Moulton, D. Hemenway, P. O'Shaughnessy, P. Vacek, B.T. Mossman
• Journal: Toxicology and Applied Pharmacology
• Published: 1996;137(1):67-74
• Cited by: 42 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Patterns of cell proliferation in lung and pleura and development of histopathologic lesions were studied in lungs from Fischer 344 rats after inhalation exposure to chrysotile or crocidolite asbestos at average airborne concentrations of approximately 8 mg/m3 air for 5 and 20 days and after 20 days of exposure followed by an additional 20 days in room air (20 + 20 days). To assess cell proliferation rats were injected with 5-bromo-2'-deoxyuridine (BrdU) at various time points after initiation of exposure to asbestos. Image analysis was used to quantitate the effects of chrysotile and crocidolite on BrdU labeling indices in the following lung compartments: (1) interstitium, (2) alveolar duct region, (3) bronchial epithelium, and (4) visceral mesothelium. With the exception of mesothelium, which exhibited significant increases in BrdU incorporation in rats exposed to crocidolite at 20 + 20 days, asbestos-induced elevations in BrdU uptake in other compartments were transient with labeling comparable to sham controls at later time points. Histopathology of rat lungs revealed fibrotic lesions of a greater extent and severity at 20 days in rats exposed to crocidolite, but fibrosis occurred in both asbestos-exposed groups after an additional 20 days in clean air (20 + 20). Quantification of fiber burden in rat lung after inhalation of comparable airborne concentrations of either fiber type demonstrated that inhalation of crocidolite asbestos led to a higher fiber retention when compared to chrysotile asbestos. Our results indicate that chrysotile and crocidolite asbestos induce different patterns of cell proliferation in lung and pleural cells. The protracted increases in BrdU labeling of mesothelial cells by crocidolite may reflect increased retention of fibers and/or inherent differences between types of asbestos.

In plain English

This was an animal experiment. Male Fischer 344 rats breathed air containing chrysotile or crocidolite asbestos, at about 8 mg per cubic meter on average, for 6 hours a day, 5 days a week. Exposures lasted 5 days, 20 days, or 20 days followed by 20 days in clean room air. Sham control rats were handled the same way in room air. A chemical label (BrdU) marked dividing cells in four parts of the lung and its covering. In most areas, increases in cell division were temporary. Bronchial lining cells showed significant increases at 5 days with both fibers. In the mesothelial cells covering the lung, chrysotile caused a reversible increase at 5 days, while the crocidolite increase became significant only after the clean-air period. At 20 days, two of eight chrysotile rats and all crocidolite rats had fibrotic lesions. After the clean-air period, both groups showed Grade 1 or 2 asbestosis. At each time point, lungs held three- to fourfold more crocidolite fibers than chrysotile fibers. The authors concluded that crocidolite was unique in inducing mesothelial cell division after protracted periods of time.

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: subchronic inhalation experiment in rats (animal experiment) comparing chrysotile and crocidolite with sham controls
• Who was studied: Male Fischer 344 rats, 4 to 6 weeks old on arrival, from the National Institutes of Health. Three experiments were run with 4 rats per group per time period, at the University of Vermont.
• Exposure: Inhaled NIEHS reference samples of chrysotile or crocidolite asbestos at average airborne concentrations of approximately 8 mg per cubic meter. Exposure ran 6 hours a day, 5 days a week, for 5 days, 20 days, or 20 days followed by an additional 20 days in room air. Sham controls were kept in room air.
• Main results:
  • Bronchial epithelium: statistically significant but transient increases in BrdU uptake at 5 days after exposure to both chrysotile and crocidolite.
  • Interstitium: statistically significant increases in BrdU labeling at 20 days with both fiber types. Apparent elevations at 5 days and at 20 + 20 days were not significant because of variability between animals.
  • Alveolar duct region: no statistically significant increases between groups at individual time points. In crocidolite-exposed groups, labeling showed a significant linear trend of decrease over time.
  • Visceral mesothelium, chrysotile: statistically significant and reversible increases in BrdU labeling at 5 days.
  • Visceral mesothelium, crocidolite: labeling did not become statistically significant until 20 days of exposure plus 20 days in room air.
  • Histopathology at 20 days, chrysotile: two of eight chrysotile-exposed rats had focal Grade 1 fibrotic lesions.
  • Histopathology at 20 days, crocidolite: all crocidolite-exposed rats had Grade 1 or Grade 2 fibrotic lesions.
  • Histopathology at 20 + 20 days: both chrysotile- and crocidolite-exposed rats showed Grade 1 or 2 asbestosis.
  • Histopathology at 5 days: no fibrosis was observed.
  • Fiber burden: in both groups, lung fiber burden rose during the 20-day exposure and declined after 20 days in room air.
  • Fiber burden: crocidolite fiber numbers in lung were three- to fourfold higher than chrysotile fiber numbers at each time point.
  • Fiber burden: no asbestos fibers were found in lung digests from sham control rats.
• The authors' conclusion: The authors concluded that increases in cell proliferation were transient in most compartments after either type of asbestos. They concluded that crocidolite was unique in inducing proliferation of mesothelial cells after protracted periods of time, which may reflect greater fiber retention and/or inherent differences between asbestos types.
• Limitations the authors state:
  • Variability between animals meant that apparent increases in interstitial labeling at 5 days and at 20 + 20 days could not be shown to be statistically significant.

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Crocidolite, Pleura, Epithelium, Mesothelium, Histopathology, Fibrosis, Fiber Burden.

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