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:

Sequential Biochemical Alteration to Antifolate Resistance in L121O Leukaemia

Abstract

ANTIFOLATE resistant, transplantable, murine tumours are most often characterized by a single change involving either the transport of drug1 or the level of dihydrofolate reductase2–5. This is understandable if one accepts the idea that multiple genetic events leading to an involvement of more than one physiological site rarely occur simultaneously. In two cases, where both physiological properties were altered6,7, the development of resistance probably occurred in a step-wise manner8. We have demonstrated this type of sequential alteration in resistance at both the physiological and cytogenetic level during repeated transplantation of a subline of L1210 leukaemia.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. Fischer, G. A., Biochem. Pharmacol., 11, 1233 (1960).

    Article  Google Scholar 

  2. Hakala, M. T., Zakrzewski, S. F., and Nichol, C. A., J. Biol. Chem., 236, 952 (1961).

    CAS  PubMed  Google Scholar 

  3. Friedkin, M., Crawford, E., Humphreys, S. R., and Goldin, A., Cancer Res., 22, 600 (1962).

    CAS  PubMed  Google Scholar 

  4. Misra, D. K., Humphreys, S. R., Friedkin, M., Goldin, A., and Crawford, E. J., Nature, 189, 39 (1961).

    Article  CAS  ADS  Google Scholar 

  5. Schrecker, A. W., Venditti, J. M., Greenberg, N. H., Biedler, J. L., Robinson, D. L., and Hutchison, D. J., J. Nat. Cancer Inst., 31, 557 (1963).

    CAS  PubMed  Google Scholar 

  6. Roberts, D., Wodinsky, I., and Hall, T. C., Cancer Res., 25, 1899 (1965).

    CAS  PubMed  Google Scholar 

  7. Kessel, D., Hall, T. C., Roberts, D., and Wodinsky, I., Science, 150, 752 (1965).

    Article  CAS  ADS  Google Scholar 

  8. Law, L. W., Nature, 169, 628 (1952).

    Article  CAS  ADS  Google Scholar 

  9. Hutchison, D. J., Robinson, D. L., Martin, D., Ittensohn, O. L., and Dillenberg, J., Cancer Res., 22, 57 (1962).

    PubMed  Google Scholar 

  10. Biedler, J. L., Schrecker, A. W., and Hutchison, D. J., J. Nat. Cancer Inst., 31, 575 (1963).

    CAS  PubMed  Google Scholar 

  11. Biesele, J. J., Biedler, J. L., Hutchison, D. J., in Genetics and Cancer, 295 (Austin University Texas Press, 1959).

    Google Scholar 

  12. Sirotnak, F. M., Kurita, S., and Hutchison, D. J., Cancer Res. (in the press).

  13. Osborn, M. J., and Huennekens, F. M., J. Biol. Chem., 233, 969 (1958).

    CAS  PubMed  Google Scholar 

  14. Hutchison, D. J., Ittensohn, O. L., and Bjerregaard, M. R., Exp. Cell Res., 42, 157 (1966).

    Article  CAS  Google Scholar 

  15. Sirotnak, F. M., Sargent, M. G., and Hutchison, D. J., J. Bacteriol., 93, 309 (1967).

    Article  CAS  Google Scholar 

  16. Werkheiser, W. C., J. Biol. Chem., 236, 888 (1961).

    CAS  Google Scholar 

  17. Lineweaver, H., and Burk, D., J. Amer. Chem. Soc., 56, 658 (1934).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

SIROTNAK, F., KURITA, S., SARGENT, M. et al. Sequential Biochemical Alteration to Antifolate Resistance in L121O Leukaemia. Nature 216, 1236–1237 (1967). https://doi.org/10.1038/2161236a0

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/2161236a0

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