Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1967 Jan 1;125(1):17–31. doi: 10.1084/jem.125.1.17

SUPPRESSION OF MURINE LEUKEMIAS BY L-ASPARAGINASE

INCIDENCE OF SENSITIVITY AMONG LEUKEMIAS OF VARIOUS TYPES: COMPARATIVE INHIBITORY ACTIVITIES OF GUINEA PIG SERUML-ASPARAGINASE AND ESCHERICHIA COLI L-ASPARAGINASE

Edward A Boyse 1, Lloyd J Old 1, H A Campbell 1, Louise T Mashburn 1
PMCID: PMC2138337  PMID: 5334543

Abstract

A survey of 109 recently derived leukemias of the mouse revealed that sensitivity to suppression by guinea pig serum is a common property of transplanted leukemias of certain classes. The sensitive leukemias included five that arose spontaneously in mice of strains with a low incidence of leukemia and 21 that were induced by X-radiation. Two GPS-sensitive leukemias were not more sensitive than a GPS-resistant leukemia to a range of standard chemotherapeutic agents. The effectiveness of L-asparaginase EC-2 from Escherichia coli in suppression of the GPS-sensitive leukemia EARAD1 depends upon the conditions of assay. Whereas it is not inhibitory when administered as a single dose at the time of inoculation of the leukemia it is considerably more effective than GPS when used in the treatment of established leukemia. Permanent cures of 7-day generalized transplants of EARAD1 can be effected by the administration of 2000 or more units of EC-2. Immunological factors apparently do not contribute to cure as treated survivors are fully susceptible to rechallenge with minimal numbers of cells from the same leukemia. Reinoculated survivors with progressively growing transplants have been successfully retreated with EC-2. The blood clearance of EC-2 L-asparaginase injected into mice is much more rapid than that of GPS L-asparaginase. After intraperitoneal inoculation of the EC-1 L-asparaginase, which does not have leukemia-inhibitory activity, only very low levels of enzyme activity could be detected in the serum. The effectiveness of EC-2 from E. coli and its availability from a virtually limitless source will make it possible to extend the study of inhibition of leukemias and other tumors by L-asparaginase to species other than small rodents.

Full Text

The Full Text of this article is available as a PDF (773.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AINIS H., JAMESON E., RYAN R. M. Action of guinea pig serum and human gamma globulin on the growth of a rat tumor. Science. 1956 Nov 16;124(3229):980–981. doi: 10.1126/science.124.3229.980. [DOI] [PubMed] [Google Scholar]
  2. BOYSE E. A., OLD L. J., STOCKERT E. Inhibitory effect of guinea pig serum on a number of new leukaemias in mice. Nature. 1963 May 25;198:800–800. doi: 10.1038/198800a0. [DOI] [PubMed] [Google Scholar]
  3. BROOME J. D. Evidence that the L-asparaginase of guinea pig serum is responsible for its antilymphoma effects. I. Properties of the L-asparaginase of guinea pig serum in relation to those of the antilymphoma substance. J Exp Med. 1963 Jul;118:99–120. doi: 10.1084/jem.118.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BROOME J. D. Evidence that the L-asparaginase of guinea pig serum is responsible for its antilymphoma effects. II. Lymphoma 6C3HED cells cultured in a medium devoid of L-asparagine lose their susceptibility to the effects of guinea pig serum in vivo. J Exp Med. 1963 Jul;118:121–148. doi: 10.1084/jem.118.1.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Broome J. D. Antilymphoma activity of L-asparaginase in vivo: clearance rates of enzyme preparations from guinea pig serum and yeast in relation to their effect on tumor growth. J Natl Cancer Inst. 1965 Dec;35(6):967–974. [PubMed] [Google Scholar]
  6. HALEY E. E., FISCHER G. A., WELCH A. D. The requirement for L-asparagine of mouse leukemia cells L5178Y in culture. Cancer Res. 1961 May;21:532–536. [PubMed] [Google Scholar]
  7. HERBUT P. A., KRAEMER W. H. The effects of animal serums on lymphosarcoma 6C3HED in C3H mice. Am J Pathol. 1958 Jul-Aug;34(4):767–774. [PMC free article] [PubMed] [Google Scholar]
  8. HOLMQUIST N. D. Effect of normal sera of several related rodents on 6C3HED lymphoma in vivo. Proc Soc Exp Biol Med. 1963 Jun;113:444–445. doi: 10.3181/00379727-113-28391. [DOI] [PubMed] [Google Scholar]
  9. Hiramoto R., Tate C., Hamlin M. Guinea pig serum inhibitory factor and asparaginase activity. Proc Soc Exp Biol Med. 1966 Feb;121(2):597–601. doi: 10.3181/00379727-121-30840. [DOI] [PubMed] [Google Scholar]
  10. KIDD J. G. Regression of transplanted lymphomas induced in vivo by means of normal guinea pig serum. I. Course of transplanted cancers of various kinds in mice and rats given guinea pig serum, horse serum, or rabbit serum. J Exp Med. 1953 Dec;98(6):565–582. doi: 10.1084/jem.98.6.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. KIDD J. G. Regression of transplanted lymphomas induced in vivo by means of normal guinea pig serum. II. Studies on the nature of the active serum constituent: histological mechanism of the regression: tests for effects of guinea pig serum on lymphoma cells in vitro: discussion. J Exp Med. 1953 Dec;98(6):583–606. doi: 10.1084/jem.98.6.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. KWAK K. S., JAMESON E., RYAN R. M., KURTZ H. M. The effect of varying implant cell numbers on the inhibitory activity of guinea pig serum on Walker carcinosarcoma 256 in the rat. Cancer Res. 1961 Jan;21:44–47. [PubMed] [Google Scholar]
  13. MASHBURN L. T., WRISTON J. C., Jr TUMOR INHIBITORY EFFECT OF L-ASPARAGINASE FROM ESCHERICHIA COLI. Arch Biochem Biophys. 1964 May;105:450–452. doi: 10.1016/0003-9861(64)90032-3. [DOI] [PubMed] [Google Scholar]
  14. McCOY T. A., MAXWELL M., KRUSE P. F., Jr The amino acid requirements of the Jensen sarcoma in vitro. Cancer Res. 1959 Jul;19(6 Pt 1):591–595. [PubMed] [Google Scholar]
  15. OLD L. J., BOYSE E. A. ANTIGENIC PROPERTIES OF EXPERIMENTAL LEUKEMIAS. I. SEROLOGICAL STUDIES IN VITRO WITH SPONTANEOUS AND RADIATION-INDUCED LEUKEMIAS. J Natl Cancer Inst. 1963 Oct;31:977–995. [PubMed] [Google Scholar]
  16. OLD L. J., BOYSE E. A., CAMPBELL H. A., DARIA G. M. Leukaemia-inhibiting properties and L-asparaginase activity of sera from certain South American rodents. Nature. 1963 May 25;198:801–801. doi: 10.1038/198801a0. [DOI] [PubMed] [Google Scholar]
  17. Old L. J., Boyse E. A., Stockert E. The G (Gross) leukemia antigen. Cancer Res. 1965 Jul;25(6):813–819. [PubMed] [Google Scholar]
  18. SULD H. M., HERBUT P. A. GUINEA PIG SERUM AND LIVER ASPARAGINASES. PURIFICATION AND ANTITUMOR ACTIVITY. J Biol Chem. 1965 May;240:2234–2241. [PubMed] [Google Scholar]
  19. Yellin T. O., Wriston J. C., Jr Antagonism of purified asparaginase from guinea pig serum toward lymphoma. Science. 1966 Feb 25;151(3713):998–999. doi: 10.1126/science.151.3713.998. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES