Hypotheses on the Mechanisms of Carcinogenesis and Cell Transformation by Asbestos and Other Mineral Dusts

  • J. Carl Barrett
  • Patricia W. Lamb
  • Roger W. Wiseman
Part of the NATO ASI Series book series (volume 21)


Asbestos and other mineral fibers are carcinogenic to humans and animals but differ from many carcinogens in that they do not induce gene mutations. Evidence, however, exists that asbestos is a complete carcinogen, an initiator, and a promoter. Multiple mechanisms, therefore, must be operative to explain the diverse effects of asbestos fibers. Although asbestos is inactive as a gene mutagen, there is now clear evidence that it induces chromosomal mutations (aneuploidy and aberrations) in a wide variety of mammalian cells, including mesothelial cells. Asbestos also induces transformation of cells in culture, including mesothelial cells and fibroblasts. A mechanism for cell transformation, which is dependent on fiber dimension, has been proposed. The fibers are phagocytized by the cells and accumulate in the perinuclear region of the cells. When the cell undergoes mitosis, the physical presence of the fibers interferes with chromosome segregation and results in anaphase abnormalities. The transformed cells show aneuploidy and other chromosome abnormalities. These findings provide a mechanism at the chromosomal level by which asbestos and other mineral fibers might induce cell transformation and cancer. Identification of the critical target genes in asbestos carcinogenicity is required to understand further process, and recent progress in this area has been made. Results from several lines of investigation suggest that two distinct classes of genes, proto-oncogenes and tumor suppressor genes, are involved in the neoplastic process. In human mesothelioma, deletion of the short arm of chromosome 3 has been observed, which may result in the loss of a tumor suppressor gene on this chromosome. We have recently shown that an activated transforming oncogene exists in human mesotheliomas. Further molecular analysis of these cancers may help in understanding these neoplasms and the mechanisms of asbestos and other carcinogenic fibers.


Mesothelial Cell Mineral Dust Asbestos Exposure Asbestos Fiber Chrysotile Asbestos 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • J. Carl Barrett
    • 1
  • Patricia W. Lamb
    • 1
  • Roger W. Wiseman
    • 1
  1. 1.Laboratory of Molecular CarcinogenesisNational Institute of Environmental Health Sciences National Institutes of HealthUSA

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