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Laboratory of Cell Regulation, Division of Molecular Medicine, The Wadsworth Center, New York State Department of Health, Albany, New York 12201-0509 [J. G. A., R. W. C., L. A. B., C. L. R.]; University of Auckland, Private Bag 92019, Auckland, New Zealand [C. G. J., L. C. W. J.]; and Department of Biomedical Sciences, State University of New York, Albany, New York 12222 [C. L. R.]
1Asbestos has been described as a physical carcinogen in that long thin fibers are generally more carcinogenic than shorter thicker ones. It has been hypothesized that long thin fibers disrupt chromosome behavior during mitosis, causing chromosome abnormalities which lead to cell transformation and neoplastic progression. Using high-resolution time lapse video-enhanced light microscopy and the uniquely suited lung epithelial cells of the newt Taricha granulosa, we have characterized for the first time the behavior of crocidolite asbestos fibers, and their interactions with chromosomes, during mitosis in living cells. We found that the keratin cage surrounding the mitotic spindle inhibited fiber migration, resulting in spindles with few fibers. As in interphase, fibers displayed microtubule-mediated saltatory movements. Fiber position was only slightly affected by the ejection forces of the spindle asters. Physical interactions between crocidolite fibers and chromosomes occurred randomly within the spindle and along its edge. Crocidolite fibers showed no affinity toward chromatin and most encounters ended with the fiber passively yielding to the chromosome. In a few encounters along the spindle edge the chromosome yielded to the fiber, which remained stationary as if anchored to the keratin cage. We suggest that fibers thin enough to be caught in the keratin cage and long enough to protrude into the spindle are those fibers with the ability to snag or block moving chromosomes.
1 This work was supported by American Lung Association Grant RG-018-N (J. G. A.), by NIH GMS Grant R01-40198 (C. L. R.), and by National Center for Research Resources Grant RR 01219 (Department of Health and Human Services/Public Health Service) to support the Wadsworth Center's Biological Microscopy and Image Reconstruction Facility as a National Biotechnological Resource.
2 To whom requests for reprints should be addressed, at the Laboratory of Cell Regulation, Division of Molecular Medicine, The Wadsworth Center, Albany, NY 12201-0509.
Received 10/ 6/94. Accepted 12/15/94.
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