Advertisement

Studies on the Control of Asparagine Biosynthesis in Mammalian Tissues

  • M. K. PattersonJr.
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 33)

Abstract

Among certain malignant tissues, sensitivity to L-asparaginase (ASNase)1 appears to be related to the nutritional requirement and biosynthesis of L-asparagine (ASN) [7, 9, 14]. With other malignant or normal tissues the relationship is not clear. From the early studies of the in vivo effects of ASNase by Kidd [10] and the in vitro nutritional requirements for ASN by McCoy et al. [11] and others [3, 15], it became apparent that under certain injection regimes or culturing conditions nutritional variants could be derived from the parent population. These variants no longer required ASN for growth and were resistant to ASNase. A similar phenomenon now appears to prevail following the clinical use of ASNase on human malignancies. A second anomoly existed in normal tissues. Those normal tissues tested showed no requirement for ASN and a resistance to ASNase, but only limited L-asparagine synthetase (ASN SYN) [4, 8, 17, 20].

Keywords

Mammalian Tissue Asparagine Synthetase Cellular Parameter Nutritional Variant Relative Specific Activity 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Arfin, S. M.: Asparagine synthesis in the chick embryo liver. Biochim. biophys. Acta (Amst.) 136, 233–244 (1967).CrossRefGoogle Scholar
  2. 2.
    Becker, F. F., Broome, J. D.: L-Asparaginase: Inhibition of early mitosis in regenerating rat liver. Science 156, 1602–1603 (1967).PubMedCrossRefGoogle Scholar
  3. 3.
    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. 118, 121–148, (1963).PubMedCrossRefGoogle Scholar
  4. 4.
    — Studies on the mechanism of tumor inhibition by L-asparaginase. J. exp. Med. 127, 1055–1072 (1968).PubMedCrossRefGoogle Scholar
  5. 5.
    Schwartz, J. H.: Differences in the production of L-asparagine in asparaginasesensitive and-resistant lymphoma cells. Biochim. biophys. Acta (Amst.) 138, 637–639 (1967).Google Scholar
  6. 6.
    Dolowy, W. C., Schrek, R., Henson, D., Cornet, J., Brown, E.: Effects of guineapig serum on the Walker 256. Nature 218, 1028–1031 (1968).PubMedCrossRefGoogle Scholar
  7. 7.
    Hill, J. M., Roberts, J., Loeb, E., Khan, A., MacLellan, A., Hill, R. W.: L-asparaginase therapy for leukemia and other malignant neoplasms. J. Amer. med. Ass. 202, 882–888 (1967).CrossRefGoogle Scholar
  8. 8.
    Holcenberg, J. S.: Guinea pig asparagine synthetase. Biochim. biophys. Acta (Amst.) 185, 228–238 (1969).Google Scholar
  9. 9.
    Horowitz, B., Madras, B. K., Meister, A., Old, L. J., Boyse, E. A., Stockert, E.: Asparagine synthetase activity of mouse leukemias. Science 160, 533–535 (1968).PubMedCrossRefGoogle Scholar
  10. 10.
    Kidd, J. G.: Effects of arsenic azoproteins on mouse lymphoma cells in vivo with observations on the effects of other antilymphoma agents, and on the susceptibility of these effects of lymphoma cells of various types. J. exp. Med. 108, 665–684 (1958).PubMedCrossRefGoogle Scholar
  11. 11.
    McCoy, T. A., Maxwell, M., Irvine, E., Sartorelli, A. C.: Two nutritional variants of cultured Jensen sarcoma cells. Proc. Soc. exp. Biol. (N. Y.) 100, 862–865 (1959).Google Scholar
  12. 12.
    Kruse, P. F., Jr.: The amino acid requirements of the Jensen sarcoma in vitro. Cancer Res. 19, 591–595 (1959).PubMedGoogle Scholar
  13. 13.
    Neuman, R. E., McCoy, T. A.: The dual requirement of the Walker carcinosarcoma 256 in vitro for asparagine and glutamine. Science 124, 124–125 (1956).PubMedCrossRefGoogle Scholar
  14. 14.
    Oettgen, H. F., Old, L. J., Boyse, E. A., Campbell, H. A., Philips, F. S., Clarkson, B. D., Tallal, L., Leeper, R. D., Schwartz, M. K., Kim, J. H.: Inhibition of leukemias in man by L-asparaginase. Cancer Res. 27, 2619–2631 (1967).PubMedGoogle Scholar
  15. 15.
    Patterson, M. K., Jr., Conway, E., Whittle, W., McCoy, T. A.: In vitro effects of guinea pig serum on the Jensen, JA-1 and JA-2 sarcomas. Proc. Soc. exp. Biol. (N. Y.) 119, 5–9 (1965).Google Scholar
  16. 16.
    Conway, E., Whittle, W., McCoy, T. A. — Maxwell, M. D., Conway, E.: Studies on the asparagine requirement of the Jensen sarcoma and the derivation of its nutritional variant. Cancer Res. 29, 296–300 (1969).PubMedGoogle Scholar
  17. 17.
    Conway, E., Whittle, W., McCoy, T. A. Maxwell, M. D., Conway, E. — Orr, G. R.: L-asparagine biosynthesis by nutritional variants of the Jensen sarcoma. Biochem. biophys. Res. Commun. 26, 228–233 (1967).PubMedCrossRefGoogle Scholar
  18. 18.
    Conway, E., Whittle, W., McCoy, T. A. Maxwell, M. D., Conway, E. Orr, G. R. — Asparagine biosynthesis by the Novikoff hepatoma. Isolation, purification, property, and mechanism studies of the enzyme system. J. biol. Chem. 243, 376–380 (1968).PubMedGoogle Scholar
  19. 19.
    Conway, E., Whittle, W., McCoy, T. A. Maxwell, M. D., Conway, E. Orr, G. R. — Regeneration, tumor, dietary, and L-asparaginase effects on asparagine biosynthesis in rat liver. Cancer Res. 29, 1179–1183 (1969).PubMedGoogle Scholar
  20. 20.
    Prager, M. D., Bachynsky, N.: Asparagine synthetase in normal and malignant tissues: correlation with tumor sensitivity to asparaginase. Arch. Biochem. 127, 645–654 (1968).PubMedCrossRefGoogle Scholar
  21. 21.
    Russell, D. H., Snyder, S. H.: Amine synthesis in regenerating rat liver: extremely rapid turnover of Ornithine decarboxylase. Mol. Pharmacol. 5, 253–262 (1969).PubMedGoogle Scholar
  22. 22.
    Taylor, E. W.: Control of DNA synthesis in mammalian cells in culture. Exp. Cell Res. 40, 316–332 (1965).PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin • Heidelberg 1970

Authors and Affiliations

  • M. K. PattersonJr.
    • 1
  1. 1.Biomedical DivisionThe Samuel Roberts Noble Foundation, Inc.ArdmoreUSA

Personalised recommendations