Advertisement

Chemotherapy pp 159-166 | Cite as

Streoptozotocin, Chlorozotocin and Related Nitrosourea Antitumour Agents

  • Phillip S. Schein
  • Tom Anderson
  • Mary G. McMenamin
  • Joan Bull

Abstract

In 1959, 1 -methyl-1 -nitroso-3-nitroguanidine (MNNG) was found to increase the life span of mice bearing leukaemia L1210 ( 1). While MNNG did not have sufficient activity to warrant extensive clinical testing, the demonstration of antitumour effect gave impetus for further evaluation of the N-nitroso class of compounds as potential antineoplastic agents. In 1961 1-methyl-1-nitrosourea (MNU) was reported to be not only more effective against intraperitoneally implanted L1210 than MNNG, but also was capable of penetrating the blood-brain barrier; MNU produced limited but reproducible antitumour activity in mice with intracerebral leukaemic cells ( 1). Since that time over 300 aIkyInitrosourea compounds have been screened for antitumour activity, the majority of the synthetic work having been undertaken by Montgomery, Johnston and co-workers at the Southern Research Institute (3).

Keywords

White Blood Cell Count Antitumour Activity Pyridine Nucleotide Bone Marrow Toxicity L1210 Leukaemia 
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.
    Skipper, H.E., Schabel, F.M. Jr., Trader, M.W. et al. (1961). Experimental evaluation of potential anticancer agent. VI. Anatomical distribution of leukaemic cells and failure of chemotherapy. Cancer Res., 21, 1154–1164.PubMedGoogle Scholar
  2. 2.
    Skipper, H.E., Schabel, F.M., Jr., and Wilcox, W.S. (1964). Experimental evaluation of potential anticancer agents. XII. On the criteria and kinetics associated with “curability” of experimental leukemia. Canc. Chemotherapy Rep., 35, 1–111.Google Scholar
  3. 3.
    Carter, S.K. (1973). An overview of the status of the nitrosoureas in other tumors. Cancer Chemotherapy Rep., 4, 35–46.Google Scholar
  4. 4.
    Walker, M.D. (1973). Nitrosoureas in central nervous system tumors. Cancer Chemotherapy Rep., 4, 21–26.Google Scholar
  5. 5.
    Moertel, C.G. (1973). Therapy of advanced gastrointestinal cancer with the nitrosoureas. Cancer Chemotherapy Rep., 4, 27–34.Google Scholar
  6. 6.
    Schein, P.S., O’Connell, M.J., Blom, J. et al. (1974). Clinical antitumor activity and toxicity of streptozotocin (NSC 85998). Cancer, 34, 993–1000.PubMedCrossRefGoogle Scholar
  7. 7.
    Herr, R.R., Jahnke, H.K. and Argoudelis, A.D. (1967). The structure of streptozotocin. J. Am. Chem. Soc, 89, 4808–4809.PubMedCrossRefGoogle Scholar
  8. 8.
    Schein, P.S., Cooney, D.A. and Vernon, M.L. (1967). The use of nicotinamide to midify the toxicity of streptozotocin diabetes without loss of antitumor activity. Cancer Res., 27, 2324–2332.PubMedGoogle Scholar
  9. 9.
    Schein, P.S. and Loftus, S. (1968). Streptozotocin: depression of mouse liver pyridine nucleotides. Cancer Res., 28, 1501–1506.PubMedGoogle Scholar
  10. 10.
    Schein, P.S., Cooney, D.A., McMenamin, M.G. and Anderson, T. (1973). Streptozotocin diabetes: further studies on the mechanisms of depression of nicotinamide adenine dinucleotide concentrations in mouse pancreatic islets and liver. Biochem. Pharmacol, 22, 2625–2631.CrossRefGoogle Scholar
  11. 11.
    Schein, P.S. (1969). 1-Methyl-1-nitrosourea and dialkylnitrosamine depression of nicotinamide adenine dinucleotide. Cancer Res., 29, 1226–1232.PubMedGoogle Scholar
  12. 12.
    Anderson, T., McMenamin, M.G. and Schein, P.S. (1975). Diabetogenic activity of deoxy-2-[(ethylnitrosoamino) carbonyl amino]-D-glucopyranose. Biochem. Pharmacol. 24, 746–747.PubMedCrossRefGoogle Scholar
  13. 13.
    Anderson, T., Schein, P.S., McMenamin, M.G. and Cooney, D.A. (1974). Streptozotocin diabetes: correlation with extent of depression of pancreatic islet nicotenamide adenine dinucleotide. J. Clin. Invest., 54, 672–677.PubMedCrossRefGoogle Scholar
  14. 14.
    Schein, P.S., McMenamin, M. and Anderson, T. (1973). 3-Tetraacetyl glucopyranose-2-yl)-1-(2-chlorethyl)-1-nitrosourea, an antitumor agent with modified bone marrow toxicity. Cancer Res., 33, 2005–2009.PubMedGoogle Scholar
  15. 15.
    Anderson, T., McMenamin, M.G. and Schein, P.S. (1975). Chlorozotocin, 2-(3-(2-chlorethyl)-3-nitrosoureido)-D-glucopyranose, an antitumor agent with modified bone marrow toxicity. Cancer Res., 35, 761–765.PubMedGoogle Scholar
  16. 16.
    Montgomery, J.A., James, R., McCaleb, G.S. and Johnston, T.P. (1967). The modes of decomposition of 1,3-bis(2-chloroethyl-1-nitrosourea and related compounds. J. Med. Chem. 10, 668–674.PubMedCrossRefGoogle Scholar
  17. 17.
    Cowens, W., Brundratt, R. and Colvin, M. (1975). Mechanism of action of bischloroethyl nitrosourea. Proc. Am. Assoc. Cancer Res., 66, 100.Google Scholar
  18. 18.
    Wheeler, G.P., Bowdon, B.J., Grimsley, J.A. and Lloyd, H.H. (1974). Interrelationships of some chemical, physiochemical, and biological activities of several 1-(2-haloethyl)-1-nitrosoureas. Cancer Res., 34, 194–200.PubMedGoogle Scholar
  19. 19.
    Schein, P.S., Bull, J., McMenamin, M.G. and Macdonald, J.S. ( 1975). DNA synthesis by human bone after incubation with BCNU or chlorozotocin (DCNU, NSC-178248). Proc. Am. Assoc. Cancer Res., 66, 122.Google Scholar

Copyright information

© Plenum Press, New York 1976

Authors and Affiliations

  • Phillip S. Schein
    • 2
    • 1
  • Tom Anderson
    • 2
    • 1
  • Mary G. McMenamin
    • 2
    • 1
  • Joan Bull
    • 2
    • 1
  1. 1.Medicine BranchNational Cancer InstituteBethesdaUSA
  2. 2.Division of Medical OncologyGeorgetown University School of MedicineWashington, D.C.USA

Personalised recommendations