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.
This paper will also appear in the Proceedings of the 29th Hanford Symposium on Health and the Environment, “Indoor Radon and Lung Cancer: Reality or Myth?” (E T. Cross, editor), Battelle Press
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Armitage, P. and R. Doll. The Age Distribution of Cancer and a Multistage Theory of Carcinogenesis. Br. J. 8: 1–12 (1954).
Knudson, A. G. Mutation and Cancer: Statistical Study of Retinoblastoma. Proc. Natl. Acad. of Sciences U.S.A. 68: 820–823 (1971).
Knudson, A. G. Hereditary Cancer, Oncogenes and Antioncogenes. Cancer Res. 45: 1437–1443 (1985).
Moolgavkar, S. H. and A. Dewanji. Biologically-Based Models for Cancer Risk Assessment: A Cautionary Note. Risk Analysis 8: 5–6 (1988).
Ames, B. N. and L. S. Gold. Tbo Many Rodent Carcinogenes: Mitogenesis Increases Mutagenesis. Science 249: 970–971 (1990).
Cohen, S. M. and L. B. Ellwein. Cell Proliferation in Carcinogenesis. Science 249: 1007–1011 (1990).
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).
Comings, D. E. A General Theory of Carcinogenesis. Proc. Natl. Acad. of Science U.S.A. 70: 3324–3328 (1973).
Moolgavkar, S. H. and A. G. Knudson. Mutation and Cancer: A Model for Human Carcinogenesis. JNCI 67: 15–23 (1981).
Moolgavkar, S. H. and A. G. Knudson. Two-Event Model for Carcinogenesis: Biological, Mathematical and Statistical Considerations. Risk Analysis 10: 323–341 (1990).
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).
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).
Stanbridge, E. J. Identifying Timor Suppressor Genes in Human Colorectal Cancer. Science 247: 12–13 (1990).
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).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Plenum Press, New York
About this chapter
Cite this chapter
Moolgavkar, S.H. (1991). Carcinogenesis Models: An Overview. In: Glass, W.A., Varma, M.N. (eds) Physical and Chemical Mechanisms in Molecular Radiation Biology. Basic Life Sciences, vol 58. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-7627-9_14
Download citation
DOI: https://doi.org/10.1007/978-1-4684-7627-9_14
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-7629-3
Online ISBN: 978-1-4684-7627-9
eBook Packages: Springer Book Archive