Advertisement

Carcinogenesis Models: An Overview

  • Suresh H. Moolgavkar
Part of the Basic Life Sciences book series (BLSC, volume 58)

Abstract

Biologically based mathematical models of the process of carcinogenesis are not only an essential part of a rational approach to quantitative cancer risk assessment, but also raise fundamental questions about the nature of the events leading to malignancy. In this paper two such models are reviewed. The first is the multistage model proposed by Armitage and Doll in the 1950s. The larger part of the paper is devoted to a discussion of the two-mutation model proposed by Moolgavkar and colleagues. This model is a generalization of the idea of recessive oncogenesis proposed by Knudson, and has been shown to be consistent with a large body of epidemiological and experimental data. The usefulness of the model is illustrated by analysis of a large experimental data set in which rats exposed to radon develop malignant lung tumors.

Keywords

Total Exposure Exposure Rate Indoor Radon Intermediate Cell Wait Time Distribution 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Armitage, P. and R. Doll. The Age Distribution of Cancer and a Multistage Theory of Carcinogenesis. Br. J. 8: 1–12 (1954).Google Scholar
  2. 2.
    Knudson, A. G. Mutation and Cancer: Statistical Study of Retinoblastoma. Proc. Natl. Acad. of Sciences U.S.A. 68: 820–823 (1971).CrossRefGoogle Scholar
  3. 3.
    Knudson, A. G. Hereditary Cancer, Oncogenes and Antioncogenes. Cancer Res. 45: 1437–1443 (1985).PubMedGoogle Scholar
  4. 4.
    Moolgavkar, S. H. and A. Dewanji. Biologically-Based Models for Cancer Risk Assessment: A Cautionary Note. Risk Analysis 8: 5–6 (1988).PubMedCrossRefGoogle Scholar
  5. 5.
    Ames, B. N. and L. S. Gold. Tbo Many Rodent Carcinogenes: Mitogenesis Increases Mutagenesis. Science 249: 970–971 (1990).PubMedCrossRefGoogle Scholar
  6. 6.
    Cohen, S. M. and L. B. Ellwein. Cell Proliferation in Carcinogenesis. Science 249: 1007–1011 (1990).PubMedCrossRefGoogle Scholar
  7. 7.
    Friend, S. H., R. Bernards, S. Rogelj, R. A. Weinberg, J. M. Rapaport, D. M. Albert, and T. P. Dryja. A Human DNA Segment with Properties of the Gene That Predisposes to Retinoblastoma and Osteosarcoma. Nature 323: 643–646 (1986).PubMedCrossRefGoogle Scholar
  8. 8.
    Comings, D. E. A General Theory of Carcinogenesis. Proc. Natl. Acad. of Science U.S.A. 70: 3324–3328 (1973).CrossRefGoogle Scholar
  9. 9.
    Moolgavkar, S. H. and A. G. Knudson. Mutation and Cancer: A Model for Human Carcinogenesis. JNCI 67: 15–23 (1981).Google Scholar
  10. 10.
    Moolgavkar, S. H. and A. G. Knudson. Two-Event Model for Carcinogenesis: Biological, Mathematical and Statistical Considerations. Risk Analysis 10: 323–341 (1990).PubMedCrossRefGoogle Scholar
  11. 11.
    Hennings, H., R. Shores, M. L. Wenk, E. F. Spangler, R. Tàrone, and S. H. Yuspa. Malignant Conversion of Mouse Skin Tumors Is Increased by Timor Initiators and Unaffected by Timor Promoters. Nature 304: 67–69 (1983).PubMedCrossRefGoogle Scholar
  12. 12.
    Scherer, E., A. W. Feringa, and P. Emmelot. Induction of Neoplastic Foci Within Islands of Precancerous Liver Cells in the Rat. In Models, Mechanism and Etiology of Timor Promotion, M. Borzsonyi, N. E. Day, K. Lapis, and H. Yamasaki, eds. IARC Scientific Publications 56, Lyon, France (1984).Google Scholar
  13. 13.
    Stanbridge, E. J. Identifying Timor Suppressor Genes in Human Colorectal Cancer. Science 247: 12–13 (1990).PubMedCrossRefGoogle Scholar
  14. 14.
    Moolgavkar, S. H., F. T Cross, E. G. Luebeck, and G. E. Dagle. A wo-Mutation Model for Radon-Induced Lung ‘Minors in Rats. Radiat. Res. 121: 28–37 (1990).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Suresh H. Moolgavkar
    • 1
  1. 1.Fred Hutchinson Cancer Research CenterSeattleUSA

Personalised recommendations