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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)

Abstract

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.

Keywords

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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References

  1. Babu KA, Lakkad BC, Nigam SK, Bhatt DK, Karnik AB, Thakore KN, Kashyap SK, Chatterjee SK (1980) In vitro cytological and cytogenetic effects of an Indian variety of chrysotile asbestos. Environ Res 21:416–422PubMedCrossRefGoogle Scholar
  2. Barrett JC, Ts’o POP (1978) Evidence for the progressive nature of neoplastic transformation in vitro. Proc Natl Acad Sci USA 75: 3761–3765PubMedCrossRefGoogle Scholar
  3. Barrett JC, Hesterberg TW, Thomassen DG (1984) Use of cell transformation systems for carcinogenicity testing and mechanistic studies of carcinogenesis. Pharmacological Reviews 36: 53S - 70SPubMedGoogle Scholar
  4. Barrett JC, Hesterberg TW, Oshimura M, Tsutsui T (1985) Role of chemically induced mutagenic events in neoplastic transformation of Syrian hamster embryo cells. In Barrett JC and Tennant RW (eds) Carcinogenesis–A Comprehensive Survey: Mannalian Cell Transformation: Mechanisms of Carcinogenesis and Assays for Carcinogens. New York Raven Press, Vol. 9, pp 123–137Google Scholar
  5. Barrett JC, Wiseman RW (1987) Cellular and molecular mechanisms of multistep carcinogenesis: relevance to carcinogen risk assessment. Environ Health Perspec 76: 65–70CrossRefGoogle Scholar
  6. Barrett JC (1987) Relationship between mutagenesis and carcinogenesis. In Barrett JC (ed) Mechanisms of Environmental Carcinogenesis: Role of Genetic and Epigenetic Changes. Boca Raton CRC Press, Vol. I, pp 129–142Google Scholar
  7. Barrett JC, Lamb PW, Wiseman RW (1989) Multiple mechanisms for the carcinogenic effects of asbestos and other mineral fibers. Environ Health Perspec. In press.Google Scholar
  8. Chamberlain M, Tarmy EM (1977) Asbestos and glass fibers in bacterial mutation tests. Mutat Res 43: 159–164PubMedCrossRefGoogle Scholar
  9. DiPaolo JA, DeMarinis AJ, Doniger J (1983) Asbestos and benzo(a)pyrene synergism in the transformation of Syrian hamster embryo cells. Pharmacology 27: 65–73PubMedCrossRefGoogle Scholar
  10. Gibas Z, Li FP, Antman KH, Bernai S, Stahel R, Sandberg AA (1986) Chromosome changes in malignant mesothelioma. Cancer Genet Cytogenet 20: 191–201PubMedCrossRefGoogle Scholar
  11. Hammond EC, Selikoff IJ, Seidman H (1979) Asbestos exposure, cigarette smoking and death rates. Ann NY Acad Sci 330: 473–490.PubMedCrossRefGoogle Scholar
  12. Harrington JS (1981) Fiber carcinogenesis: Epidemiologic observations and the Stanton hypothesis. J Natl Cancer Inst 67: 977–988Google Scholar
  13. Hesterberg TW, Barrett JC (1984) Dependence of asbestos-and mineral dust-induced transformation of mammalian cells in culture on fiber dimension. Cancer Res 44: 2170–2180PubMedGoogle Scholar
  14. Hesterberg TW, Barrett JC (1985) Induction by asbestos fibers of anaphase abnormalities: Mechanism for aneuploidy induction and possibly carcinogenesis. Carcinogenesis 6: 473–475PubMedCrossRefGoogle Scholar
  15. Hesterberg TW, Oshimura M, Barrett JC (1985) Transformation of mammalian cells in culture by asbestos and other mineral dusts: A mechanism involving chromosomal mutation. In: In vitro Effects of Mineral Dusts. Third International Workshop, NATO ASI Series, Vol. G3 (Beck EG, Bignon J, eds), Springer-Verlag Berlin, pp 185–196Google Scholar
  16. Hesterberg TW, Brody AR, Oshimura M, Barrett JC (1986a) Asbestos and silica induce morphological transformation of mammalian cells in culture: A possible mechanism. In: Silica, Silicosis, and Cancer (Goldsmith DF, Winn DM, Shy CM, eds), Praeger Press New York, pp 177–190Google Scholar
  17. Hesterberg TW, Butterick CJ, Oshimura M, Brody AR, Barrett JC (1986b) Role of phagocytosis in Syrian hamster cell transformation and cytogenetic effects induced by asbestos and short and long glass fibers. Cancer Res 46: 5795–5802PubMedGoogle Scholar
  18. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man (1977) Vol. 14, Asbestos. International Agency for Research on Cancer, Lyon FranceGoogle Scholar
  19. Jaurand MC (1989) A particulate state carcinogenesis: Recent data on the mechanisms of action of fibers. IARC Publications 90: 54–73PubMedGoogle Scholar
  20. Jaurand MC, Kheuang L, Magne L, Bignon J (1986) Chromosomal changes induced by chrysotile fibers or benzo-3,4-pyrene in rat pleural mesothelial cells. Mutation Res 169: 141–148PubMedCrossRefGoogle Scholar
  21. Kok K, Osinga J, Carritt B, Davis MB, van der Hout AH, van der Veen AY, Landsvater RM, de Leij LFMH, Berendsen HH, Postmus PE, Poppema S, Buys CMCM (1987) Deletion of a DNA sequence at the chromosomal region 3p21 in all major types of lung cancer. Nature 330: 578–581Google Scholar
  22. Lavappa KS, Fu MM, Epstein SS (1975) Cytogenetic studies on chrysotile asbestos. Environ Res 10: 165–173PubMedCrossRefGoogle Scholar
  23. Lechner JF, Tokiwa T, LaVeck M, Benedict WF, Banks-Schlegel S, Yeager Jr H, Banerjee A, Harris CC (1985a) Asbestos-associated chromosomal changes in human mesothelial cells. Proc Natl Acad Sci USA 82: 3884–3888PubMedCrossRefGoogle Scholar
  24. Lechner JF, Tokiwa T, Yeager Jr H, Harris CC (1985b) Asbestos-associated chromosomal changes in human mesothelial cells. In: In vitro Effects of Mineral Dusts. Third International Workshop, NATO ASI Series, Vol. G3 (Beck EG, Bignon J, eds), Springer-Verlag Berlin, pp 197–202Google Scholar
  25. Linnainmaa K, Gerwin B, Pelin K, Jantunen K, LaVeck M, Lechner JF, Harris CC (1986) Asbestos-induced mesothelioma and chromosomal abnormalities in human mesothelial cells In vitro. NIOSH Symposium Extended AbstractGoogle Scholar
  26. Lu Y-P, Lasne C, Lowy R, Chouroulinkov I (1988) Use of the orthogonal design method to study the synergistic effects of asbestos fibers and 12–0-tetradecanoylphorbol-13-acetate (TPA) in the BALB/3T3 cell transformation system. Mutagenesis 3: 355–372PubMedCrossRefGoogle Scholar
  27. Mikalsen SO, Rivedal E, Sanner T (1988) Morphological transformation of Syrian hamster embryo cells induced by mineral fibres and the alleged enhancement of benzo(a)pyrene. Carcinogenesis 9: 891–899PubMedCrossRefGoogle Scholar
  28. Mossman BT, Craighead JE (1980) Asbestos-induced epithelial changes in organ cultures of hamster trachea: Inhibition by retinyl methyl ether. Science 207: 311–313PubMedCrossRefGoogle Scholar
  29. Mossman BT, Light WG, Wei ET (1983) Asbestos: mechanisms of toxicity and carcinogenicity in the respiratory tract. Ann Rev Pharmacol Toxicol 23: 595–602CrossRefGoogle Scholar
  30. Mossman BT, March JP (1985) Mechanisms of toxic injury by asbestos fibers: Role of oxygen free radicals. In: In vitro Effects of Mineral Dusts. Third International Workshop, NATO ASI Series, Vol. G3 (Beck EG, Bignon J, eds), Springer-Verlag Berlin pp 66–74Google Scholar
  31. Mossman BT, Marsh JP, Doherty J, Gilbert R, Hill S (1987) Implication of active oxygen species as second messengers of asbestos toxicity. Drug Chem Toxicol 10: 157–180PubMedCrossRefGoogle Scholar
  32. National Research Council (1984) Asbestiform Fibers: Nonoccupational Health Risks. National Academy Press, Washington, DCGoogle Scholar
  33. Oshimura M, Hesterberg TW, Tsutsui T, Barrett JC (1984) Correlation of asbestos-induced cytogenetic effects with cell transformation of Syrian hamster embryo cells in culture. Cancer Res 44: 5017–5022PubMedGoogle Scholar
  34. Oshimura M, Hesterberg TW, Barrett JC (1986) An early, nonrandom karyotypic change in immortal Syrian hamster cell lines transformed by asbestos: trisomy of chromosome 11. Cancer Genet Cytogenet 22: 225–237PubMedCrossRefGoogle Scholar
  35. Patérour MJ, Bignon J, Jaurand MC (1985) In vitro transformation of rat pleural mesothelial cells by chrysotile and/or benzoa-pyrene. Carcinogenesis 6:523–529PubMedCrossRefGoogle Scholar
  36. Patérour MJ, Renier A, Bignon J, Jaurand MC (1985) Induction of transformation in cultured rat pleural mesothelial cells by chrysotile fibers. In: In vitro Effects of Mineral Dusts. Third International Workshop, NATO ASI Series, Vol. G3 (Beck EG, Bignon J, eds), Springer-Verlag Berlin, pp 203–207Google Scholar
  37. Peto J, Henderson BE, Pike MC (1982a) Trends in mesothelioma incidence in the United States and the forecast epidemic due to asbestos exposure during World War II. Quantification of Occupation Cancer 9: 51–69Google Scholar
  38. Peto J, Seidman H, Selikoff IJ (1982b) Mesothelioma mortality in asbestos workers: Implications for models of carcinogenesis and risk assessment. Br J Cancer 45: 124–135PubMedCrossRefGoogle Scholar
  39. Popescu NC, Chahinian AP, DiPaolo JA (1988) Nonrandom chromosome alterations in human malignant mesothelioma. Cancer Res 48: 142–147PubMedGoogle Scholar
  40. Renier A, Fleury J, Monchaux G, Nebut M, Bignon J, Jaurand MC (1989) Toxicity of an attapulgite sample studied in vivo and in vitro. In Bignon J, Peto J, and Saracci R (eds) Non-occupational Exposure to Mineral Fibres. ARC Scientific Publications No. 90, 180–184Google Scholar
  41. Selikoff IJ, Hammond EC, Churg J (1968) Asbestos exposure, smoking, and neoplasia. J Amer Medical Assoc 204: 101–110CrossRefGoogle Scholar
  42. Sincock AM, Seabright M (1975) Induction of chromosome changes in Chinese hamster cells by exposure to asbestos fibers. Nature (Lond) 257: 56–58CrossRefGoogle Scholar
  43. Stanton MF, Layard M, Tegeris A, Miller E, May M, Morgan E, Smith A (1981) Relation of particle dimension to carcinogenicity in amphibole asbestoses and other fibrous minerals. J Natl Cancer Inst 67: 965–975PubMedGoogle Scholar
  44. Stenman C, Olofsson K, Mansson T, Hagmar B, Mark J (1986) Chromosomes and chromosomal evolution in human mesotheliomas as reflected in sequential analyses of two cases. Herreditas 105: 233–239CrossRefGoogle Scholar
  45. Topping DC, Nettesheim P (1980) Two-stage carcinogenesis studies with asbestos in Fischer 344 rats. J Natl Cancer Inst 3: 627–630Google Scholar
  46. Valerio F, DeFerran M, Ottaggio L, Repetto E, Santi L (1980) Cytogenetic effects of Rhodesian chrysotile on human lymphocytes in vitro. In: Biological Effects of Mineral Fibers, Vol. I (Wagner JC, ed), International Agency for Research on Cancer, Lyon France, pp 485–489Google Scholar
  47. Wagner JC, Berry G, Skidmore JW, Timbrell V (1974) The effects of the inhalation of asbestos in rats. Br J Cancer 29: 252–269PubMedCrossRefGoogle Scholar
  48. Wang NS, Jaurand MC, Magne L, Kheuang L, Pinchon MC, Bignon J (1987) The interactions between asbestos fibers and metaphase chromosomes of rat pleural mesothelial cells in culture. Am J Pathol 126: 343–349PubMedGoogle Scholar
  49. Whang-Peng J, Kao-Shan CS, Lee EC, Bunn PA, Carney DN, Gazdar AT, Minna JD (1982) Specific chromosome defect associated with human small-cell lung cancer: deletion 3p14–23. Science (Wash DC) 215: 181–182CrossRefGoogle Scholar

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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