Molecular Mechanisms of Metal Carcinogenesis in Experimental Animals

  • Max Costa
Part of the Biological Methods book series (BM)


The molecular mechanisms of metal carcinogenesis are not well understood. However, the data available suggest that metals cause cancer by a mechanism that is similar to the way in which organic carcinogens induce transformation, i.e., by binding to cellular DNA or associated proteins, which then induce mutations. Whether the metal compound or free metal is converted to an “ultimate” carcinogen is not known, but several different experiments suggest that the ionization state and the crystalline structure of the metal are important factors in determining its ability to cause cancer. If a metal causes cancer by direct “genetic mechanisms” involving mutations in the primary sequency of DNA, it must be able to distribute directly to the nucleus and remain there to make contact with DNA. Experimental evidence suggests that carcinogenic metals do in fact enter the nuclei preferentially, and bind to nucleic acids and proteins within the nuclear structure. Additionally, experiments...


Thymidine Kinase Metal Compound Ames Test Carcinogenic Activity Thymidylate Synthetase 
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  1. 1.
    Sirover, M. A., and L. A. Loeb, Alteration in the fidelity of DNA synthesis by beryllium. Proc. Amer. Assn. Cancer Res. 17: Abstr. #451, 113, 1976.Google Scholar
  2. 2.
    Sirover, M. A., and L. A. Loeb, Metal-induced infidelity during DNA synthesis. Proc. Natl Acad. Sci. USA 73: 2331–2335, 1976.PubMedCrossRefGoogle Scholar
  3. 3.
    Sirover, M. A., and L. A. Loeb, On the fidelity of DNA replication. Effect of metal activators during synthesis with avian myeloblastosis virus DNA polymerase. J. Biol. Chem. 252: 3605–3610, 1977.PubMedGoogle Scholar
  4. 4.
    Sirover, M. A., and L. A. Loeb, Infidelity of DNA synthesis in vitro: Screening for potential metal mutagens or carcinogens. Science 194: 1434–1436, 1976.PubMedCrossRefGoogle Scholar
  5. 5.
    Loeb, L. A., M. A. Sirover, L. A. Weymouth, D. K. Dube, G. Seal, S. S. Agarwal, and E. Katz, Infidelity of DNA synthesis as related to mutagenesis and carcinogenesis. J. Toxicol Environ. Health. 2: 1297–1304, 1977.PubMedCrossRefGoogle Scholar
  6. 6.
    Loeb, L. A., M. A. Sirover, And S. S. Agarwal, Infidelity of DNA synthesis as related to mutagenesis and carcinogensis. In: Inorganic and Nutritional Aspects of Cancer, G. N. Schrauzer, Ed. Plenum, N.Y., 1978, Chap. 8, pp. 103–115.Google Scholar
  7. 7.
    Truhaut, R., C. Boudene, and J-Y. Le Talaer, Fixation preferentielle du beryllium dans les noyaux de foie des rats a forte activite mitotique. Ann. Biol. Clin. 23: 45–47, 1965.Google Scholar
  8. 8.
    Witschi, H. P., and W. N Aldridge, Uptake, distribution, and binding of beryllium to organelles of the rat liver cell. Biochem, J. 106: 811–820, 1968.Google Scholar
  9. 9.
    Witschi, H. P., Inhibition of DNA synthesis in regenerating rat liver by beryllium. Lab Invest. 19: 67–70, 1968.PubMedGoogle Scholar
  10. 10.
    Witschi, H. P., Effects of beryllium on deoxyribonucleic acid synthesizing enzymes in regenerating rat liver. Biochem. J. 120:623–634, 1970.PubMedGoogle Scholar
  11. 11.
    Witschi, H. P., and P. Marchand, Interference of beryllium with enzyme induction in rat liver. Toxicol. Appl. Pharmacol. 20: 565–572, 1971.PubMedCrossRefGoogle Scholar
  12. 12.
    Marcotte, J., and Witschi, H. P., Synthesis of RNA and nuclear proteins in early regenerating rat livers exposed to beryllium. Res. Commun. Chem. Pathol. Pharmacol. 3: 100–104, 1972.Google Scholar
  13. 13.
    Reiner, E., Binding of beryllium to protein. In: A Symposium on Mechanisms of Toxicity, W. N. Aldridge, ed. Macmillan, London, 1971, pp. 111–125.Google Scholar
  14. 14.
    Heath, J. C., and M. Webb, Content and intracellular distribution of the inducing metal in the primary rhabdomyosarcomata induced in the rat by cobalt, nickel, and cadmium. Brit. J. Cancer 21: 768–779, 1967.PubMedCrossRefGoogle Scholar
  15. 15.
    Webb, M., J. C. Heath, and T. Hopkins, Intranuclear distribution of the inducing metal in primary rhabdomyosarcomata induced in the rat by nickel, cobalt, and cadmium. Brit. J. Cancer 26: 274–278, 1972.PubMedCrossRefGoogle Scholar
  16. 16.
    Venitt, S., and L. S. Levy, Mutagenicity of chromates in bacteria and its relevance to chromate carcinogenesis. Nature 250: 493–495, 1974.PubMedCrossRefGoogle Scholar
  17. 17.
    Webb, M., and S. M. Weinzierl, Uptake of 63Ni2+ from its complexes with proteins and other ligands by mouse dermal fibroblasts in vitro. Brit. J. Cancer 26: 292–298, 1972.PubMedCrossRefGoogle Scholar

Copyright information

© The Humana Press Inc. 1980

Authors and Affiliations

  • Max Costa
    • 1
  1. 1.University of Texas Medical School at Houston

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