A murine model of asbestosis

Our plain-English summary of A murine model of asbestosis, by B.E. Bozelka, P. Sestini, H.R. Gaumer, et al (The American Journal of Pathology, 1983).

The study

• Authors: B.E. Bozelka, P. Sestini, H.R. Gaumer, Y. Hammad, C.J. Heather, J.E. Salvaggio
• Journal: The American Journal of Pathology
• Published: 1983;112(3):326-37
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Balb/c mice were exposed to aerosolized chrysotile fibers and evaluated as a host for the study of asbestos-induced pulmonary disease. Histologically, an initial macrophage reaction was found to progress to "asbestos body" formation and diffuse focal interstitial fibrosis within 1 year of a chronic exposure period. This reaction was most intense in areas adjacent to respiratory bronchioles and alveolar ducts. Two morphologically distinct tumors at the pulmonary visceral surface were also discovered among a high percentage of asbestos-exposed mice. Bronchoalveolar lavage demonstrated an eventual alteration of the retrievable cell populations among the dusted animals. Evaluation of systemic B-lymphocyte activity suggested a stimulation of this cell subset following chrysotile inhalation. These results demonstrate that subsequent to chronic asbestos exposure, the mouse develops pulmonary and immunologic changes very similar to those noted in human asbestosis.

In plain English

This was an animal experiment at Tulane University, New Orleans. Female Balb/c mice breathed UICC standard chrysotile asbestos through their noses at an average of 10.9 mg per cubic meter, 2 hours a day, 5 days a week, for up to 2.5 months. Control mice sat in the apparatus without asbestos. After 30 days, lungs of 5 exposed mice held an average of 39.7 micrograms of chrysotile. Macrophages (scavenger cells) gathered early, and scarring followed. One year after exposure ended, all exposed mice examined had scattered patches of lung scarring (fibrosis); coated fibers called "asbestos bodies" were a common finding. Control lungs were normal. Lung tumors at or just beneath the lung surface were found in 92% of 25 exposed mice examined 12 to 18 months after exposure, versus 10% of 20 controls. The authors likened the more common tumor type to human adenocarcinoma and a rarer type to asbestos-induced mesothelioma. Exposed mice also showed altered lung-wash cells and higher blood levels of some antibodies. The authors concluded the mouse is a desirable host for studying asbestos-induced lung disease.

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 study in mice, with unexposed control mice)
• Who was studied: Female Balb/c mice, 2 to 3 months old, raised in the authors' animal facility at Tulane University, New Orleans. A group of 90 mice was exposed, plus an additional group of 10 mice given a single exposure for the lavage study. Subgroups were examined at different time points.
• Exposure: UICC standard reference sample of chrysotile asbestos, given by nose-only inhalation at an average of 10.9 mg chrysotile per cubic meter, 2 hours a day, 5 days per week, for up to 2.5 months (75 days). A separate group of 10 mice received a single exposure of 8 mg chrysotile per cubic meter for 3 hours.
• Main results:
  • After 30 days of exposure, X-ray diffraction of the lungs of 5 exposed mice found an average of 39.7 plus or minus 2.3 micrograms of chrysotile. No chrysotile fibers were detected in control tissues.
  • After 4 to 5 days of exposure, the first change seen in exposed mice was an influx of macrophages near respiratory bronchioles and alveolar ducts.
  • One year after the last exposure, all of the exposed mice examined had focal fibrotic lesions scattered throughout the five lobes of the lung. These were most common around terminal respiratory bronchioles and alveolar ducts. Age-matched unexposed control mice had normal lungs.
  • The authors described asbestos body formation as a common finding in the lungs of chrysotile-exposed mice. They did not report it as present in every mouse. These coated fibers resembled the "asbestos bodies" found in exposed humans and were seen both inside and outside cells. The authors called this somewhat unexpected, because asbestos body formation has generally been associated with amphibole asbestos.
  • Among 25 exposed mice examined 12 to 18 months after exposure ended, 92% had lung tumors, compared with 10% of 20 control mice (Table 1). Tumors arose at or just below the visceral pleura. In exposed mice most were 3 to 6 mm across and often multiple, and a few took over entire lobes and invaded the parietal pleura and rib cage. No primary tumors or metastases were found in other organs. Tumors in control mice were always single and small (1 to 2 mm).
  • Two microscopic tumor types were seen in exposed mice. The authors described the more common type as very similar to human adenocarcinoma. They described the less common type as comparable, by gross and light-microscopic analysis, to asbestos-induced mesotheliomas in animals and man. Tumors in control mice resembled the first type.
  • Mice given a single 3-hour exposure at 8 mg per cubic meter showed no significant change in lung-wash (bronchoalveolar lavage) cells at any time point, compared with controls.
  • In mice exposed for 75 days and washed 1 year later, alveolar macrophages fell from a mean of 93.8% in 10 control mice to 76.4% in 13 exposed mice. Lymphocytes rose from 5.0% to 13.9%, and polymorphonuclear leukocytes rose from 1.3% to 9.1%. The authors reported these increases as significant. (The text prints the last two figures as "13.907o" and "9.1%1o".)
  • After 40 days of exposure, before fibrosis was evident, exposed mice had significantly higher serum IgM (31.62 vs 21.12 mg/dl), IgG2b (267.56 vs 207.88) and IgA (81.61 vs 61.00) than controls, each p less than 0.05. IgG1 (703.6 exposed vs 786.7 control) was not significantly different.
  • Unstimulated spleen cells from exposed mice showed a background antibody-forming (plaque-forming cell) response five times greater than unstimulated control cells. Adding the B-cell stimulant LPS did not raise it further. Control cells showed a 10-fold increase with LPS.
• The authors' conclusion: The authors concluded that the Balb/c mouse is a desirable host for studying how asbestos causes lung disease. In their view, chrysotile-exposed mice developed lung and immune changes very similar to human asbestosis. They stated that, to their knowledge, this was the first report of fibrosis, tumor formation and altered immune reactivity in a single animal species after inhaling asbestos.
• Limitations the authors state:
  • The authors stated that future studies need to examine the type (phenotype) of the induced tumors more closely, along with fiber dose and the relationship between fibrosis and tumors.
  • The authors stated that more in-depth immune testing is needed to tell whether the B-cell changes are side effects or actually part of how the disease develops.

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Macrophage, Asbestos Body Formation, Interstitial Fibrosis, Bronchoalveolar Lavage (BAL), Asbestos Exposure.

Related studies

• Chronological assessment of asbestos exposure on cell composition in murine lung — B.E. Bozelka, S.B. Lehrer, et al. (1992)
• Fractionated low-dose radiotherapy primes the tumor microenvironment for immunotherapy in a murine mesothelioma model — R.A. D'Alonzo, S. Keam, et al. (2025)
• Establishment of a murine model of malignant mesothelioma — M.R. Davis, L.S. Manning, et al. (1992)
• A commercially available preparation of Staphylococcus aureus bio-products potently inhibits tumour growth in a murine model of mesothelioma — S.M. Lansley, J.F. Varano Della Vergiliana, et al. (2014)
• Gene expression profiles reveal increased mClca3 (Gob5) expression and mucin production in a murine model of asbestos-induced fibrogenesis — T. Sabo-Attwood, M. Ramos-Nino, et al. (2005)
• The role of the receptor for advanced glycation end-products in a murine model of silicosis — L. Ramsgaard, J.M. Englert, et al. (2010)

Browse more research in The American Journal of Pathology, or return to medical research.