Bone marrow alterations induced in mice with inhalation of chrysotile asbestos

Our plain-English summary of Bone marrow alterations induced in mice with inhalation of chrysotile asbestos, by G.A. Boorman, J.H. Dean, M.I. Luster, et al (Toxicology and Applied Pharmacology, 1984).

The study

• Authors: G.A. Boorman, J.H. Dean, M.I. Luster, B. Adkins, A. Brody, H.L. Hong
• Journal: Toxicology and Applied Pharmacology
• Published: 1984;72(1):148-58
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The effect of chrysotile asbestos exposure on bone marrow and immune parameters was examined in mice at 2, 12, and 26 weeks following a 3-day inhalation exposure. Ultrastructural examination revealed that the fibers were deposited primarily at alveolar duct bifurcations within the centriacinar region of the lung. Histological pulmonary changes were minimal, but by 26 weeks early asbestosis characterized by clusters of macrophages and minimal fibrosis were present in the centriacinar region of the lung. Lymphoproliferative responses, antibody levels, and number of plaque forming cells were not significantly altered in exposed mice. Pulmonary macrophages, but not peritoneal macrophages, showed evidence of activation in the chrysotile-exposed mice at 26 weeks following exposure. The most striking change was the depression of the number of bone marrow pluripotent stem cells (CFU-S) and marrow granulocyte macrophage progenitors (CFU-GM) which were lower at all three postexposure examinations. It is felt that the depression of bone marrow progenitors in asbestos-exposed mice may have relevance to the leukopenia reported in workers with occupational history of asbestos exposure.

In plain English

In this laboratory experiment, female mice aged 6 to 8 weeks breathed chrysotile asbestos dust for 6 hours a day on 3 consecutive days, at a measured concentration of 11.3 plus or minus 2.54 mg per cubic meter. They were compared with control mice at 2, 12 and 26 weeks afterwards. Fibers settled mainly at alveolar duct branchings deep in the lung. Lung changes were mild. By 26 weeks there were early changes consistent with asbestosis, including clusters of macrophages and very minimal fibrosis. In exposed mice, bone marrow progenitor cells (CFU-GM) were 65% of control values at 2 weeks and 67% at 26 weeks. Stem cells (CFU-S) were reduced by 28% at 2 weeks and 31% at 26 weeks. White blood cells were significantly increased at 2 weeks, but the increase at 26 weeks was not significant. Lymphocyte and antibody measures showed no significant differences. The authors concluded that the bone marrow changes may have relevance to low white cell counts reported in presumably healthy asbestos-exposed workers. They noted that the lack of immune effects might reflect testing for only 26 weeks.

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 inhalation experiment: mice exposed to chrysotile asbestos for a short period, compared with controls at 2, 12 and 26 weeks after exposure
• Who was studied: Female hybrid mice (C57BL/6N crossed with C3H), 6 to 8 weeks old, weighing 18 to 22 g, studied at the National Toxicology Program, NIEHS, Research Triangle Park, North Carolina. Seven mice per group for the bone marrow, blood and immune measurements; 20 per group for the lung macrophage measurements. Total number of mice not stated.
• Exposure: Whole-body inhalation of chrysotile asbestos (Johns-Manville, Quebec) for 6 hours a day on 3 consecutive days, at 11.3 plus or minus 2.54 mg per cubic meter. Controls breathed filtered room air.
• Main results:
  • Right after exposure, fibers in exposed mice were deposited mainly at alveolar duct bifurcations in the centriacinar region of the lung.
  • In exposed mice at 12 weeks, the inflammatory lung changes seen at 2 weeks had regressed.
  • In exposed mice at 26 weeks, there were early changes consistent with asbestosis: clusters of alveolar macrophages and very minimal fibrosis.
  • In exposed mice, granulocyte macrophage progenitors (CFU-GM) were 65% of control values at 2 weeks and 67% at 26 weeks.
  • In exposed mice, pluripotent stem cells (CFU-S) were reduced by 28% at 2 weeks and by 31% at 26 weeks, with no evidence of recovery.
  • By 26 weeks, exposed mice had a 26% increase in bone marrow cells per femur compared with controls.
  • Circulating white blood cells were significantly increased in exposed mice at 2 weeks. At 26 weeks they were increased, but not significantly.
  • At 26 weeks, exposed mice had a significant increase in red blood cells and packed cell volume.
  • Cells washed from the lungs of exposed mice were roughly doubled in number at 2 and 12 weeks.
  • At 26 weeks, lung macrophages from exposed mice showed increased tumor cell cytostasis (99%), a marker of macrophage activation.
  • This macrophage activation was not seen at 2 or 12 weeks, and was not seen in peritoneal macrophages.
  • At no time point were there significant differences between exposed and control mice in lymphoproliferative responses, plaque forming cells, serum immunoglobulins or delayed hypersensitivity reactions.
• The authors' conclusion: The authors concluded that the depression of bone marrow progenitor cells may have relevance to the leukopenia (low white blood cell counts) reported in presumably healthy workers with occupational asbestos exposure.
• Limitations the authors state:
  • The authors suggested the absence of immune effects may reflect testing the mice for only up to 26 weeks; in humans, immune dysfunction often occurs years after exposure.
  • The authors' suggested explanation for the bone marrow depression (prostaglandin secretion by macrophages) was not tested, because prostaglandin levels were not measured.
  • The authors stated that further study is needed on the role of alveolar macrophages in blood cell production in asbestos-exposed mice.
  • Blood parameters were not measured at 12 weeks.

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Asbestos Exposure, Macrophage, Fibrosis, STEM, Occupational History.

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