Induction of metaphase and anaphase/telophase abnormalities by asbestos fibers in rat pleural mesothelial cells in vitro

Our plain-English summary of Induction of metaphase and anaphase/telophase abnormalities by asbestos fibers in rat pleural mesothelial cells in vitro, by M. Yegles, L. Saint-Etienne, A. Renier, et al (American Journal of Respiratory Cell and Molecular Biology, 1993).

The study

• Authors: M. Yegles, L. Saint-Etienne, A. Renier, X. Janson, M.C. Jaurand
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1993;9(2):186-91
• Cited by: 50 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The cytogenetic effects of asbestos fibers on rat pleural mesothelial cells were studied in vitro. Crocidolite UICC significantly enhanced aneuploidy and produced few structural chromosome aberrations, whereas anatase, an isomorphic particle, induced no numerical or structural changes. Mitomycin C (300 nM) produced a tenfold increase in abnormal anaphases compared with controls. Asbestos produced anaphase/telophase abnormalities in a concentration-dependent manner. The majority of the abnormalities involved lagging chromosomes. Crocidolite UICC induced abnormalities at a dose of 7.0 micrograms/cm2, whereas Canadian chrysotile did so at 1.0 to 2.0 micrograms/cm2. When the response was assessed by the number of long and thin fibers per cm2 (length > 8 microns; diameter < or = 0.25 microns), crocidolite UICC produced more abnormalities than Canadian chrysotile at all concentrations. On a per-weight basis, these findings differ from those obtained after intrapleural inoculation, as crocidolite induced more mesotheliomas than chrysotile; however, on a per-fiber basis, the in vitro and in vivo effects were similar. These results show that anaphase/telophase analysis is sensitive and complementary to metaphase analysis, and suggest that asbestos might produce cell transformation by inducing chromosome missegregation and aneuploidy.

In plain English

This laboratory study exposed rat pleural mesothelial cells (cells lining the chest cavity) grown in culture to crocidolite (UICC sample), Canadian chrysotile, or anatase, a non-asbestos titanium dioxide particle, for 48 hours. The drug mitomycin C served as a positive comparison. The authors looked for chromosome damage in dividing cells. Crocidolite significantly increased cells with an abnormal chromosome number at 4 and 6 micrograms per square centimetre but caused few structural breaks. Anatase caused neither. In the later stages of cell division, crocidolite significantly increased abnormal divisions at 7.0 micrograms per square centimetre, and chrysotile did so at 1.0, 1.5 and 2.0. Anatase did not. Most abnormalities were lagging chromosomes. By weight, chrysotile produced more abnormalities. Counting only long, thin fibers (longer than 8 micrometres and 0.25 micrometres wide or less), crocidolite was more effective. The authors concluded that this test is sensitive and complements standard chromosome analysis. They also concluded that asbestos might transform cells by causing chromosomes to separate wrongly. They noted their cells were not in ideal conditions for detecting structural damage.

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: In vitro laboratory experiment (cytogenetic study of cultured cells)
• Who was studied: Rat pleural mesothelial cells (RPMC) from a cell line established in the authors' laboratory (INSERM U139, Créteil, France), used up to 20 passages. 50 metaphases were examined per treatment in the metaphase test, and 150 anaphases/telophases were scored per treatment in the anaphase/telophase test.
• Exposure: Crocidolite (UICC), Canadian chrysotile, and anatase (titanium dioxide, a non-fibrous comparison particle), each for 48 hours. Mitomycin C at 300 nM was the positive reference. Metaphase test doses: anatase 2, 5 and 10 µg/cm2; crocidolite 1, 2, 4 and 6 µg/cm2. Anaphase/telophase test doses: anatase 5, 7.5 and 10 µg/cm2; chrysotile 0.5 to 2.0 µg/cm2; crocidolite 0.9 to 7 µg/cm2.
• Main results:
  • Crocidolite significantly increased metaphases with numerical chromosome changes (aneuploidy) at 4 and 6 µg/cm2 (P less than 0.01). Anatase produced no significant increase in aneuploidy.
  • Structural chromosome aberrations increased with crocidolite only at 6 µg/cm2, mainly chromosome breaks. Anatase did not induce chromosomal changes.
  • In control cultures, 96 plus or minus 1.6% of anaphase/telophases were normal (mean of nine experiments).
  • Mitomycin C (300 nM) produced a 10-fold increase in abnormal anaphases compared with untreated controls.
  • Anatase did not significantly increase abnormal anaphase/telophases.
  • Crocidolite significantly increased anaphase abnormalities at 7.0 µg/cm2. Canadian chrysotile did so at 1.0, 1.5 and 2.0 µg/cm2.
  • On a per-weight basis, Canadian chrysotile produced more abnormalities than crocidolite.
  • By total fiber count: crocidolite at 37.1 million total fibers per cm2 (7 µg/cm2) induced about 20% abnormal anaphases. Canadian chrysotile at 69.0 million total fibers per cm2 (2.0 µg/cm2) produced 26.7%.
  • Counting only fibers of the dimensions defined by Stanton and colleagues (longer than 8 µm, diameter 0.25 µm or less), crocidolite was more efficient than chrysotile.
  • The most common abnormality was lagging chromatin.
  • Chromosome bridges were significantly increased by mitomycin C but not by crocidolite.
  • The authors compared these results with earlier intrapleural injection studies in rats (not part of this study). They reported a qualitative correlation between the cell and animal findings when the relevant number of fibers was used for the comparison.
• The authors' conclusion: The authors concluded that anaphase/telophase analysis is sensitive and complementary to metaphase analysis. They also concluded that the results suggest asbestos might produce cell transformation by inducing chromosome missegregation and aneuploidy.
• Limitations the authors state:
  • The experiments were not done in the best conditions for observing structural chromosomal aberrations, because the cells were mainly at their second division.
  • Fiber dispersion differed between the preparation methods used for animal and cell studies, which affects comparisons between them.
  • Animal tumor studies usually test one high dose, while cell studies test a range of relatively low doses.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Crocidolite, UICC, Mitomycin C, Chrysotile, Mesothelioma.

Related studies

• Role of fibre characteristics on cytotoxicity and induction of anaphase/telophase aberrations in rat pleural mesothelial cells in vitro: correlations with in vivo animal findings — M. Yegles, X. Janson, et al. (1995)
• The interactions between asbestos fibers and metaphase chromosomes of rat pleural mesothelial cells in culture. A scanning and transmission electron microscopic study — N.S. Wang, M.C. Jaurand, et al. (1987)
• Induction by asbestos fibers of anaphase abnormalities: mechanism for aneuploidy induction and possibly carcinogenesis — T.W. Hesterberg, J.C. Barrett (1985)
• Metaphase and anaphase analysis of V79 cells exposed to erionite, UICC chrysotile and UICC crocidolite — L.D. Palekar, J.F. Eyre, et al. (1987)
• Analysis of cell cycle disruptions in cultures of rat pleural mesothelial cells exposed to asbestos fibers — V. Levresse, A. Renier, et al. (1997)
• Effect of simian virus large T antigen expression on cell cycle control and apoptosis in rat pleural mesothelial cells exposed to DNA damaging agents — V. Levresse, S. Moritz, et al. (1998)

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