Long crocidolite asbestos fibers cause polyploidy by sterically blocking cytokinesis

Our plain-English summary of Long crocidolite asbestos fibers cause polyploidy by sterically blocking cytokinesis, by C.G. Jensen, L.C. Jensen, C.L. Rieder, et al (Carcinogenesis, 1996).

The study

• Authors: C.G. Jensen, L.C. Jensen, C.L. Rieder, R.W. Cole, J.G. Ault
• Journal: Carcinogenesis
• Published: 1996;17(9):2013-21
• Cited by: 53 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos has been described as a physical carcinogen in that its carcinogenic effects appear to be related primarily to fiber dimensions. It has been hypothesized that long asbestos fibers may interfere with chromosome distribution during cell division, causing genomic changes that lead to cell transformation and neoplastic progression. Using high-resolution time-lapse light microscopy and serial-section electron microscopy, we have followed individual crocidolite asbestos fibers through the later stages of cell division in LLC-MK2 epithelial cells, and have detailed for the first time their effect on cytokinesis. We found that long fibers (15-55 microgram), trapped by the cleavage furrow, sterically blocked cytokinesis, sometimes resulting in the formation of a binucleated cell. The ends of blocking fibers were usually found within invaginations of the newly formed nuclei. Nuclear envelope-fiber attachment was evident when a chromatin strand ran with the fiber into the intercellular bridge. Such strands may break, causing chromosome structural rearrangements. Our data are the first to show that individual crocidolite fibers can cause genomic changes by sterically blocking cytokinesis and that fiber length and affinity for the nuclear envelope are important factors. Such genomic changes may be among the initial events leading to asbestos-induced cancers.

In plain English

This laboratory study examined what crocidolite asbestos fibers do when cells divide. The authors added crocidolite to dishes of rhesus monkey kidney cells. They filmed individual dividing cells under a microscope (26 containing asbestos, 13 unexposed controls) and examined some with an electron microscope. Long fibers, 15 to 55 micrometers, could become caught where a dividing cell pinches in two. In seven fiber-containing cells this pinching was roughly half as fast as in nine control cells. Of 12 cells with long fibers caught this way, 4 eventually split, 6 stayed joined by a channel holding the fiber, and 2 failed to split, forming one cell with two nuclei. When 2000 cells per group were counted, abnormal nuclei increased significantly after 7 and 14 days of exposure but not after 2 days. At 14 days, 61.7% of exposed cells had normal nuclei, against 93.4% in 14-day controls. The authors concluded that single long crocidolite fibers can cause genomic changes by physically blocking cell division. They suggested this may be an early step toward asbestos-related cancers.

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 study using time-lapse video light microscopy of living dividing cells and serial-section electron microscopy, plus counts of nuclear abnormalities in exposed and unexposed cultures
• Who was studied: Cultured LLC-MK2 rhesus monkey kidney epithelial cells (a cell line, not people or animals). Filming covered 39 dividing cells: 26 containing asbestos and 13 controls. Nuclear counts covered 2000 cells in each of five culture groups (10,000 cells in total). The work was done at the Wadsworth Center, New York State Department of Health; study dates are not given.
• Exposure: International Union Against Cancer (UICC) crocidolite asbestos, added to cultures at 0.3 to 1.0 mg/ml. For the nuclear counts, cultures were exposed to 0.6 mg/ml for 2, 7 or 14 days. In 1000 measured fibers, the mean length was 8.19 micrometers and 11.4% were 15.0 to 55.0 micrometers long.
• Main results:
  • Fibers trapped in the bridge between forming daughter cells were 15 to 55 micrometers long (mean 30.4 micrometers; 27 fibers in 16 cells).
  • Asbestos-containing cells took on average 7.7 minutes to begin furrowing (pinching in), against 6.9 minutes for controls. The difference was not statistically significant (P = 0.1).
  • The average furrowing rate in seven asbestos-treated cells was about half that of nine control cells (P less than 0.0001). Over the first two-thirds of cleavage the rate was 1.17 micrometers per minute in asbestos-containing cells and 2.26 micrometers per minute in controls.
  • Twelve dividing cells with long fibers in the interzone were followed for 12 to 48 hours. Separation was delayed in all 12, and in 8 the daughter cells had not separated by the end of filming. Only 4 of the 12 completed division.
  • Six of the 12 cells completed division except for an intercellular channel that still contained the crocidolite fibers.
  • In 2 of the 12 cells, a long fiber blocked the final splitting of the cell, producing a single cell with two nuclei.
  • Fibers appeared attached to the nuclear envelope, with a strand of chromatin (chromosome material) running with the fiber into the bridge between the cells.
  • Nuclear abnormalities did not increase significantly in controls over time or after 2 days of crocidolite exposure. However, 44 instances of cells connected by fibers were seen among the 2000 cells scored at 2 days.
  • Polyploid cells (cells that were binucleated, multinucleated or had a polyploid nucleus) increased significantly between 2 and 7 days of exposure and again between 7 and 14 days.
  • Percentage of cells with normal nuclei, in order: control at 2 days 93.5, control at 14 days 93.4, crocidolite at 2 days 95.2, crocidolite at 7 days 67.4, crocidolite at 14 days 61.7. The 7- and 14-day crocidolite values were significantly different from either control (P less than 0.005).
• The authors' conclusion: The authors concluded that individual crocidolite fibers can cause genomic changes by physically (sterically) blocking cytokinesis, the final splitting of a dividing cell. They concluded that fiber length and affinity for the nuclear envelope are important factors, and suggested such changes may be among the initial events leading to asbestos-induced cancers.
• Limitations the authors state:
  • Living cells could be filmed for no more than 48 hours because of concerns for cell health in the small microperfusion chamber.
  • Furrowing rates could not be measured beyond the first two-thirds of cleavage, because fibers often prevented the bridge from narrowing further.

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite, Carcinogenic, Fiber Dimensions, Fiber Length.

Related studies

• Inhibition of cytokinesis by asbestos and synthetic fibres — C.G. Jensen, M. Watson (1999)
• Patterns of 8-hydroxydeoxyguanosine formation in DNA and indications of oxidative stress in rat and human pleural mesothelial cells after exposure to crocidolite asbestos — H. Fung, Y.W. Kow, et al. (1997)
• Bringing together evolution on serpentine and polyploidy: spatiotemporal history of the diploid-tetraploid complex of Knautia arvensis (Dipsacaceae) — F. Kolář, T. Fér, et al. (2012)
• Molecular alterations at 9q33.1 and polyploidy in asbestos-related lung cancer — P. Nymark, E. Kettunen, et al. (2009)
• Mesothelial cell proliferation and biopersistence of wollastonite and crocidolite asbestos fibers — J.L. Macdonald, A.B. Kane (1997)
• Lung mesothelial cell and fibroblast responses to pleural and alveolar macrophage supernatants and to lavage fluids from crocidolite-exposed rats — I.Y. Adamson, H. Prieditis, et al. (1997)

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