Organ Specificity and Tumor Promotion

  • Stuart H. Yuspa
  • Henry Hennings
  • Ulrike Lichti
  • Molly Kulesz-Martin
Part of the Basic Life Sciences book series


The modification of experimental carcinogenesis by agents that are not carcinogenic alone has been studied for over 40 years. Much attention has centered on compounds termed tumor promoters. Tumor promoters cause or allow the expression of the latent tumor phenotype induced in some cells by limited doses of carcinogens. Both chemical and physical stimuli can act as tumor promoters. Interest in tumor promotion is appropriate since this phase of carcinogenesis accounts for most of the latent period. For many years research in tumor promotion was confined to studies in mouse skin and limited to the use of impure reagents such as croton oil. During the last decade, broad interest in this aspect of carcinogenesis has developed largely due to the discovery of specific agents that act as tumor promoters and to the development of experimental models other than mouse skin in which promotionlike events contribute to tumor formation. Perhaps of equal importance, epidemiological studies in human cancer have suggested that a promotion phase is important in lung cancer, colon cancer, and cancer in hormonall-egulated target tissues.


Terminal Differentiation Phorbol Ester Tumor Promotion Mouse Skin Mouse Epidermis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Diamond, L., T.G. O’Brien, W.M. Baird. 1980. Tumor promoters and the mechanism of tumor promotion. Adv. Cancer Res. 32: 1–74.Google Scholar
  2. 2.
    Yuspa, S.H., U. Lichti, T. Ben, E. Patterson, H. Hennings, T.J. Slaga, N. Colburn, and W. Kelsey. 1976. Phorbolesters stimulate DNA synthesis and ornithine decarboxylase activity in mouse epidermal cell cultures. Nature 262: 402–404.PubMedCrossRefGoogle Scholar
  3. 3.
    Peraino, C., R.J.M. Fry, E. Staffeldt, and J.P. Christopher. 1975. Comparative enhancing effects of phenobarbital, amobarbital, diphenylhydantoin and dichlorodiphenyltri- chloroethane on 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat. Cancer Res. 35: 2884–2890.PubMedGoogle Scholar
  4. 4.
    Epstein, J.H. 1978. Photocarcinogenesis: A review. Natl. Cancer Inst. Monograph 50: 13–25.Google Scholar
  5. 5.
    Scribner, N.K., and J.D. Scribner. 1980. Separation of initiating and promoting effects of the skin carcinogen 7-bromomethylbenz[a]anthracene. Carcinogenesis 1: 97–100.PubMedCrossRefGoogle Scholar
  6. 6.
    Marks, F., S. Bertsch, and J. Schweizer. 1978. Homeostatic regulation of epidermal cell proliferation. Bull. Cancer 65: 207–222.Google Scholar
  7. 7.
    Shubik, P. 1950. The growth potentialities of induced skin tumors in mice. The effects of different methods of chemical carcinogenesis. Cancer Res. 10: 713–717.Google Scholar
  8. 8.
    Saffiotti, U., and P. Shubik. 1956. The effects of low concentrations of carcinogen in epidermal carcinogenesis. A comparison with promoting agents. J. Natl. Cancer Inst. 16: 961–969.Google Scholar
  9. 9.
    Verma, A.K., and R.K. Boutwell. 1980. Effects of dose and duration of treatment with the tumor promoting agent, 12–0-tetradecanoylphorbol-13-acetate on mouse skin carcinogenesis. Carcinogenesis 1: 271–276.PubMedCrossRefGoogle Scholar
  10. 10.
    Stenback, F. 1978. Life history and histopathology of ultraviolet light-induced skin tumors. Natl. Cancer Inst. Monograph 50: 57–70.Google Scholar
  11. 11.
    Raick, A.N., K. Thumm, and B.R. Chivers. 1972. Early effects of 12–0-tetradecanoylphorbol-13-acetate on the incorporation of tritiated precursor into DNA and the thickness of the interfollicular epidermis, and their relation to tumor promotion in mouse skin. Cancer Res. 32: 1562–1568.PubMedGoogle Scholar
  12. 12.
    O’Brien, T.G. 1976. The induction of ornithine decarboxylase as an early, possibly obligatory, event in mouse skin carcinogenesis. Cancer Res. 36: 2644–2653.PubMedGoogle Scholar
  13. 13.
    Lichti, U., S.H. Yuspa, and H. Hennings. S-adenosylmethionine decarboxylases in cultures treated with tumor promoters. Tumor Promotion and Cocarcinogenesis. and R.K. Boutwell, eds. Raven Press: pp. 221–232. 1978. Ornithine and mouse epidermal cell In: Mechanisms of T.J. Slaga, A. Sivak, New York.Google Scholar
  14. 14.
    Garte, S.J., and S. Belman. 1978. Effects of multiple phorbol myristate acetate treatments on cyclic nucleotide levels in mouse epidermis. Biochem. Biophys. Res. Comm. 84: 489–494.Google Scholar
  15. 15.
    lannaccone, P.M., R.L. Gardner, and H. Harris. 1978. The cellular origin of chemically induced tumors. J. Cell Sci. 29: 249–269.Google Scholar
  16. 16.
    Delclos, K.B., D.S. Nagle, and P.M. Blumberg. 1980. Specific binding of phorbol ester tumor promoters to mouse skin. Cell 19: 1025–1033.PubMedCrossRefGoogle Scholar
  17. 17.
    Lichti, U., E. Patterson, H. Hennings, and S.H. Yuspa. 1981. The tumor promoter 12–0-tetradecanoylphorbol-13-acetate induces ornithine decarboxylase in proliferating basal cells but not in differentiating cells from mouse epidermis. J. Cell Physiol. 107: 261–270.PubMedCrossRefGoogle Scholar
  18. 18.
    Yuspa, S.H., U. Lichti, D. Morgan, and H. Hennings. 1980. Chemical carcinogenesis studies in mouse epidermal cell cultures. In: Biochemistry of Normal and Abnormal Epidermal Differentiation. I.A. Bernstein and M. Seiji, eds. University of Tokyo Press: Tokyo. pp. 171–188.Google Scholar
  19. 19.
    Yuspa, S.H., P. Hawley-Nelson, J.R. Stanley, and H. Hennings. 1980. Epidermal cell culture. Transplant. Proc. 12, Suppl. 1: 114–122.Google Scholar
  20. 20.
    Hennings, H., D. Michael, C. Cheng, P. Steinert, K. Holbrook, and S.H. Yuspa. 1980. Calcium regulation of growth and differentiation of mouse epidermal cells in culture. Cell 19: 245–254.PubMedCrossRefGoogle Scholar
  21. 21.
    Kulesz-Martin, M., B. Koehler, H. Hennings, and S.H. Yuspa. 1980. Quantitative assay for carcinogen altered differentiation in mouse epidermal cells. Carcinogenesis 1: 995–1006.PubMedCrossRefGoogle Scholar
  22. 22.
    Yuspa, S.H., and D.L. Morgan. 1981. Initiation of carcinogenesis in mouse skin is associated with alterations in commitment for terminal differentiation. Nature 293: 72–74.PubMedCrossRefGoogle Scholar
  23. 23.
    Yuspa, S.H., H. Hennings, M. Kulesz-Martin, and U. Lichti. (in press). The study of tumor promotion in a cell culture model for mouse skin, a tissue which exhibits multistage carcinogenesis in vivo. In: Cocarcinogenesis and Biological Effects of Tumor Promoters. E. Hecker, ed. Raven Press: New York.Google Scholar
  24. 24.
    Yuspa, S.H., H. Hennings, and U. Lichts. (in press). Initiator and promoter induced specific changes in epidermal function and biological potential. J. Supramol. Struct.Google Scholar
  25. 25.
    Potten, C.S., and T.D. Allen. 1975. Control of epidermal proliferative units. Differentiation 3: 161–165.PubMedCrossRefGoogle Scholar
  26. 26.
    Yuspa, S.H, T.B. Ben, H. Hennings, and U. Lichti. 1980. Phorbol ester tumor promoters induce epidermal transglutaminase activity. Biochem. Biophys. Res. Comm. 97: 700–708.Google Scholar
  27. 27.
    Yuspa, S.H., T. Ben, H. Hennings, and U. Lichti. 1981. Heterogeneous response in epidermal basal cells exposed to the tumor promoter 12–0-tetradecanoylphorbol-13-acetate. Submitted for publication.Google Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Stuart H. Yuspa
    • 1
  • Henry Hennings
    • 1
  • Ulrike Lichti
    • 1
  • Molly Kulesz-Martin
    • 1
  1. 1.In Vitro Pathogenesis Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Cancer Cause and PreventionNational Cancer InstituteBethesdaUSA

Personalised recommendations