Intracellular protein binding to asbestos induces aneuploidy in human lung fibroblasts

Our plain-English summary of Intracellular protein binding to asbestos induces aneuploidy in human lung fibroblasts, by R.A. MacCorkle, S.D. Slattery, D.R. Nash, et al (Cell Motility and the Cytoskeleton, 2006).

The study

• Authors: R.A. MacCorkle, S.D. Slattery, D.R. Nash, B.R. Brinkley
• Journal: Cell Motility and the Cytoskeleton
• Published: 2006;63(10):646-57
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Exposure to the natural mineral fiber asbestos causes severe lung-damaging fibrosis and cancer, yet it continues to be used as an industrial insulating material throughout the world. When cultured human lung cells are exposed to asbestos, individual fibers are engulfed into the cytoplasm where they induce significant mitotic aberrations leading to chromosomal instability and aneuploidy. The mechanisms of how asbestosis ultimately leads to lung cancer remain unclear. However, our experiments indicate that intracellular asbestos fibers induce aneuploidy and chromosome instability by binding to a subset of proteins that include regulators of the cell cycle, cytoskeleton, and mitotic process. Moreover, precoating of fibers with protein complexes efficiently blocked asbestos-induced aneuploidy in human lung cells without affecting their uptake by cells. These results provide new evidence that asbestos fibers can contribute to significant spindle damage and chromosomal instability by binding to proteins needed for the assembly and regulation of the cytoskeleton or the cell cycle.

Copyright 2006 Wiley-Liss, Inc.

In plain English

This was a laboratory study of a human lung fibroblast cell line (CCD-18 Lu) grown in culture. No people or animals were studied. The authors exposed the cells to crocidolite asbestos, Canadian chrysotile and Calidria chrysotile, with fiberglass as the control fiber. In cells exposed to crocidolite at 5 micrograms per square centimetre for 24 hours, the authors reported a 24-fold increase in abnormalities, an eightfold increase in multipolar cells and a fivefold increase in polyploid cells (cells with extra DNA). They reported similar results with chrysotile. In cell extracts, chrysotile and crocidolite bound a selected group of proteins, including INCENP, CENP-B and beta-tubulin, which fiberglass did not bind. Coating crocidolite fibers beforehand with lung cell extract or MAP-rich tubulin reduced multinucleation and mitotic abnormalities by over 80 and 90 percent respectively. Coating with BSA did not significantly reduce them. Coated fibers were still taken up by cells. The authors concluded that protein binding is a major contributing factor to asbestos-induced aneuploidy (abnormal chromosome numbers). They noted that protein capture inside cells might occur below their detection levels.

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: Laboratory (in vitro) cell culture experiment, with microscopy and protein-binding analysis
• Who was studied: Cultured human lung fibroblast cells of the CCD-18 Lu cell line; no human subjects
• Exposure: Cape Blue crocidolite, Canadian chrysotile and Calidria chrysotile asbestos, with sonicated fiberglass as a control. The main dose was 5 micrograms per square centimetre; one experiment used 0.25 micrograms per square centimetre crocidolite for 1 week. Some fibers were precoated with proteins (BSA, lung cell extract, tubulin or MAP-rich tubulin).
• Main results:
  • In crocidolite-exposed cells (fiberglass-exposed cells were the controls), the authors reported a 24-fold increase in abnormalities, an eightfold increase in multipolar cells and a fivefold increase in polyploid cells
  • Similar results were obtained with chrysotile asbestos
  • Chrysotile and crocidolite bound a subset of proteins from lung-cell extract (including INCENP, CENP-B and beta-tubulin) that the control fiberglass did not bind
  • Precoating fibers with lung cell lysate or MAP-rich tubulin reduced multinucleation and mitotic abnormalities by over 80% and over 90% respectively
  • Precoating with BSA did not significantly reduce multinucleation and mitotic abnormalities
  • Precoated fibers were still taken up by the cells
  • Inside cells, beta-tubulin colocalized with asbestos fibers, but INCENP or CENP-B colocalization was not detected
• The authors' conclusion: The authors concluded that the binding of intracellular proteins by asbestos is a major contributing factor to asbestos-induced aneuploidy in these cells
• Limitations the authors state:
  • Capture of asbestos-binding proteins inside cells may occur below the authors' detection levels
  • Cells with micronuclei were excluded from the polyploidy assay because they were hard to distinguish from dying (apoptotic) cells

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Santa Rita mine, Joaquin Ridge near Coalinga, California

All asbestos mines

Topics

Medical terms in this study, explained in our Lexicon: Fibroblast, Mineral Fiber, Fibrosis, Lung Cancer.

Related studies

• Chrysotile asbestos induces PDGF-A chain-dependent proliferation in human and rat lung fibroblasts in vitro — J.A. Lasky, J.C. Bonner, et al. (1996)
• Refractory ceramic fibers (RCFs) induce germline aneuploidy in Drosophila oocytes — C.J. Osgood (1994)
• Induction by asbestos fibers of anaphase abnormalities: mechanism for aneuploidy induction and possibly carcinogenesis — T.W. Hesterberg, J.C. Barrett (1985)
• Detection of aneuploidy-inducing carcinogens in the Syrian hamster embryo (SHE) cell transformation assay — D.P. Gibson, M.J. Aardema, et al. (1995)
• Mineral fibers induce apoptosis in Syrian hamster embryo fibroblasts — E. Dopp, B. Nebe, et al. (1995)
• Effects of chrysotile co-exposure on BaP binding in normal human fibroblasts — M.J. Chang, N.P. Singh, et al. (1983)

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