DNA and Time in Carcinogenesis

  • M. Radman
  • R. Wagner
  • P. Jeggo


Epidemiological and experimental studies of carcinogenesis have shown that time and DNA are important factors in the process of carcinogenesis (see ref. 1–3 for review). Whereas the importance of DNA in carcinogenesis has been revealed in its multiple aspects and is incorporated in all current models of carcinogenesis, few models deal with a crucial fact of carcinogenesis, its relationship with time. This short article presents a summary of time and DNA factors involved in carcinogenesis and is structured around a simple model which predicts that specific genes exist which control the activity of cellular oncogenes (or cancer genes) and suggests strategies of how to look for such onco-regulator genes and for their products.


Latency Period Control Region Chromosomal Rearrangement Cancer Gene Cold Spring Harbor Laboratory 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1).
    Cairns, J. (1978). Cancer, Science and Society. W.H. Freeman and Co., San Francisco.Google Scholar
  2. 2).
    Peto, R. (1977). Epidemiology, multistage models and short-term mutagenicity tests. In: Origins of human cancer (Eds, H.H. Hiatt, J.D. Watson and J.A. Winsten), p. 1403, Cold Spring Harbor Laboratory Press, New York.Google Scholar
  3. 3).
    Radman, M., Jeggo, P. and Wagner, R. (1982). Chromosomal rearrangement and carcinogenesis. Mutation Res., 98, 249.PubMedCrossRefGoogle Scholar
  4. 4).
    Weinberg, R.A. (1982). Fewer and fewer oncogenes. Cell, 30, 3.PubMedCrossRefGoogle Scholar
  5. 5).
    Cooper, G.M. (1982). Cellular transforming genes. Science, 218, 801.CrossRefGoogle Scholar
  6. 6).
    Bishop, J.M. (1981). Enemies within: the genesis of retrovirus oncogenes. Cell, 23, 5.PubMedCrossRefGoogle Scholar
  7. 7).
    Cooper, G.M., Okenquist, S. and Silverman, L. (1980). Transforming activity of DNA of chemically transformed and normal cells, Nature, 284, 418.PubMedCrossRefGoogle Scholar
  8. 8).
    Rajewsky, M.F., Augenlicht, L.H., Biessmann, H., Goth, R., Hulser, D.F., Laerum, O.D. and Lomakina, L., Ya (1977). Nervous-system-specific carcinogenesis by ethyl nitrosourea in the rat: molecular and cellular aspects. In: Origins of Human cancer (Eds, H.H. Hiatt, J.D. Watson and J.A. Winsten), p. 709, Cold Spring Harbor Laboratory Press, New York.Google Scholar
  9. 9).
    Setlow, R.B. (1978). Repair deficient human disorders and cancer. Nature, 271, 713.PubMedCrossRefGoogle Scholar
  10. 10).
    Peto, R. (1979). Detection of risk of cancer to man. Proc. R. Soc. Lond. B, 205, 111.PubMedCrossRefGoogle Scholar
  11. 11).
    De Boer, P., Van Buul, P.P.W., Van Beek, R., Van Der Hoven, F.A. and Natarajan, A.T. (1977). Chromosomal radiosensitivity and karyotype in mice using cultured peripheral blood lymphocytes and comparison with system in man. Mutation Res., 42, 379.PubMedCrossRefGoogle Scholar
  12. 12).
    Kennedy, A.R., Fox, M.S., Murphy, G. and Little, J.B. (1980). Relationship between X-ray exposure and malignant transformation in C3H 10 T 1/2 cells. Proc. Natl. Acad. Sci. USA, 77, 7267CrossRefGoogle Scholar
  13. 13).
    Little, J.B. (1981). Influence of non-carcinogenic secondary factors on radiation carcinogenetic. Radiation Res., 87, 240.PubMedCrossRefGoogle Scholar
  14. 14).
    Slaga, T.J., Fisher, S.M., Nelson, K. and Gleason, G.L. (1981). Studies on the mechanism of skin tumour promotion: evidence for several stages in promotion. Proc. Natl. Acad. Sci. USA, 77, 3659.CrossRefGoogle Scholar
  15. 15).
    Kennedy, A.R. and Little, J.B. (1978). Protease inhibitors suppress radiation-induced malignant transformation in vitro. Nature, 276, 825.PubMedCrossRefGoogle Scholar
  16. 16).
    Kuroki, T. and Drevon, C. (1979). Inhibition of chemical transformation in C3H/10 T 1/2 cells by protease inhibitors. Cancer Res. 39, 2755.PubMedGoogle Scholar
  17. 17).
    Comings, D.E. (1973). A general theory of carcinogenesis. Proc. Natl. Acad. Sci. USA, 70, 3324.PubMedCrossRefGoogle Scholar
  18. 18).
    Moolgavkar, S.H. and Knudson, A.G. (1971). Mutation and cancer; a model for human carcinogenesis. J. Natl. Cancer Inst., 66, 1037.Google Scholar
  19. 19).
    Weinsten, I.B. (1980). In:. Mechanisms of toxicity and hazard evaluation (eds, B. Holmstedt, R. Lauwereys, M. Mercier and M. Roberfroid), p. 149, Elsevier/North Holland Biomedical Press, Amsterdam.Google Scholar
  20. 20).
    Bissell, M.J., Hatie, C. and Calvin, M. (1978). Is the product of the src gene a promoter? Proc. Natl. Acad. Sci. USA, 76, 348.CrossRefGoogle Scholar
  21. 21).
    Kakunaga, T. (1977). The transformation of human diploid cell by chemical carcinogens, In: Origins of human cancer (eds, H.H. Hiatt, J.D. Watson and J.A. Winsten), p. 1537. Cold Spring Harbor Laboratory Press, New York.Google Scholar
  22. 22).
    Kinsella, A.R. and Radman, M. (1978). Tumour promoter induces sister chromatid exchange: relevance to mechanisms of carcinogenesis. Proc. Natl. Acad. Sci. USA, 75, 6149.PubMedCrossRefGoogle Scholar
  23. 23).
    Kinsella, A.R. and Radman, M. (1980). Inhibition of carcinogen-induced chromosomal aberrations by an anti-carcinogenic protease inhibitor. Proc. Natl. Acad. Sci. USA, 77, 3544.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • M. Radman
    • 1
    • 2
  • R. Wagner
    • 1
  • P. Jeggo
    • 1
  1. 1.Département de Biologie MoléculaireUniversité libre de BruxellesRhode-St-GenèseBelgium
  2. 2.Institut Jacques Monod, C.N.R.S.Université Paris 7Paris, Cedex 05France

Personalised recommendations