Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Tumour promoter TPA enhances transformation of human leukocytes by Epstein–Barr virus

Abstract

TUMOUR-promoting phorbol esters have contributed to the concept of multiple-step carcinogenesis1, as illustrated in the two-stage mouse skin carcinogenesis model2. Promoters are not significantly carcinogenic when tested alone, but decrease the threshold dose of carcinogens (initiators) and reduce the latency period for tumour appearance. 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and several other diterpene esters represent potent tumour promoters3–5. Recently, it has been shown that these promoters efficiently induce persisting genomes of oncogenic herpesviruses, particularly of Epstein–Barr virus (EBV)6–8, resulting in high percentages of viral antigen and particle-positive cells. Other observations showed that TPA enhances in vitro transformation of fibroblasts previously exposed to polycyclic aromatic hydrocarbons, UV light or adenoviruses9–12. These studies prompted us to analyse the effect of TPA not only on virus induction in EBV genome-harbouring cells, but also on EBV-induced transformation of human cord blood lymphocytes. Our data show that low concentrations of TPA significantly enhance transformation of lymphocytes by EBV.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Foulds, L. Neoplastic Development (Academic, New York, 1969).

    Google Scholar 

  2. Berenblum, I. in Cancer Vol. 1 (ed. Becker, F. F.) 323–344 (Plenum, New York, 1975).

    Google Scholar 

  3. Van Duuren, B. L. Prog. exp. Tumor Res. 11, 31–68 (1969).

    Article  CAS  Google Scholar 

  4. Boutwell, R. K. CRC crit. Rev. Tox. 2, 419–443 (1974).

    Article  CAS  Google Scholar 

  5. Hecker, E. in Handbuch der Allgemeinen Pathologie, Vol. 4 (ed. Grundmann, E.) 651–675 (Springer, Berlin, 1975).

    Google Scholar 

  6. zur Hausen, H., O-Neill, F. J., Freese, U. K. & Hecker, E. Nature 272, 373–375 (1978).

    Article  ADS  CAS  Google Scholar 

  7. zur Hausen, H., Bornkamm, G. W., Schmidt, R. & Hecker, E. Proc. natn. Acad. Sci. U.S.A. 76, 782–785 (1979).

    Article  ADS  CAS  Google Scholar 

  8. Yamamoto, N., Bister, K. & zur Hausen, H. Nature 278, 553–554 (1979).

    Article  ADS  CAS  Google Scholar 

  9. Lasne, C., Gentil, A. & Chouroulinkov, I. Nature 247, 490–491 (1974).

    Article  ADS  CAS  Google Scholar 

  10. Mondal, S., Brankow, D. W. & Heidelberger, C. Cancer Res. 36, 2254–2260 (1976).

    CAS  PubMed  Google Scholar 

  11. Mondal, S. & Heidelberger, C. Nature 260, 710–711 (1976).

    Article  ADS  CAS  Google Scholar 

  12. Fisher, P. B., Weinstein, B., Eisenberg, D. & Ginsberg, H. S. Proc. natn. Acad. Sci. U.S.A. 75, 2311–2314 (1978).

    Article  ADS  CAS  Google Scholar 

  13. Miller, G. & Lipmann, M. Proc. natn. Acad. Sci. U.S.A. 70, 190–194 (1973).

    Article  ADS  CAS  Google Scholar 

  14. Yamamoto, N. & Hinuma, Y. Int. J. Cancer 17, 191–196 (1976).

    Article  CAS  Google Scholar 

  15. Katsuki, T., Hinuma, Y., Yamamoto, N., Abo, T. & Kumagai, K. Virology 83, 287–294 (1977).

    Article  CAS  Google Scholar 

  16. Yamamoto, N. & Hinuma, Y. Virology 89, 623–626 (1978).

    Article  CAS  Google Scholar 

  17. Touraine, J. L. et al. J. exp. Med. 145, 460–465 (1977).

    Article  CAS  Google Scholar 

  18. Bister, K., Yamamoto, N. & zur Hausen, H. Int. J. Cancer 23, 818–825 (1979).

    Article  CAS  Google Scholar 

  19. Macpherson, I. in Tissue Cultures (eds Kruse, P. F. & Patterson, M. K.) Ch. 7 (Academic,New York, 1973).

    Google Scholar 

  20. Böyum, A. Scand. J. chim. Invest. 21, Suppl. 97, 77–89 (1968).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

YAMAMOTO, N., HAUSEN, H. Tumour promoter TPA enhances transformation of human leukocytes by Epstein–Barr virus. Nature 280, 244–245 (1979). https://doi.org/10.1038/280244a0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/280244a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing