Biochemical Consequences of Treatment with the Adenosine Deaminase Inhibitor 2′-Deoxycoformycin

  • Rosanne M. Paine
  • J. F. Smyth
  • K. R. Harrap
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 122B)


A congenital absence of the enzyme adenosine deaminase (ADA, EC has been associated with profound T and B cell deficiencies in children, leading to immune dysfunction (1). Cohen et al (2) have demonstrated that ADA deficient children have elevated levels of 2′-deoxyadenosine triphosphate (dATP) in their erythrocytes. dATP is a known negative effector of the enzyme ribonucleotide reductase (3). In view of the finding that ADA activity is high in the blast cells of patients with T-cell acute lymphocytic leukaemia (4), an ADA inhibitor might well induce a selectively toxic event in the lymphoblast.


Adenosine Deaminase Adenosine Deaminase Activity Triplicate Assay Adenosine Deaminase Deficiency Deoxyadenosine Triphosphate 
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  1. 1.
    E.R. Giblett, J.E. Anderson, F. Cohen, B. Pollara and H.J. Meuwissen, Adenosine deaminase deficiency in two patients with severe impaired cellular immunity, Lancet 2: 1067 (1972).PubMedCrossRefGoogle Scholar
  2. 2.
    A. Cohen, R. Hirschhorn, S.D. Horowitz, A. Rubinstein, S.H. Polmar, R. Hong and D.W. Martin Jr., Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine deaminase deficiency, Proc. Natl. Acad. Sci. USA 75: 472 (1978).PubMedCrossRefGoogle Scholar
  3. 3.
    E.C. Moore and R.B. Hurlbert, Regulation of mammalian deoxy-ribonucleotide biosynthesis by nucleotides as activators and inhibitors, J. Biol. Chem. 241: 4802 (1966).PubMedGoogle Scholar
  4. 4.
    J.F. Smyth, D.G. Poplack, B.J. Holiman, B.G. Leventhal and G. Yarbro, Correlation of adenosine deaminase activity with cell surface markers in acute lymphoblastic leukaemia, J. Clin. Invest. 62: 710 (1978).PubMedCrossRefGoogle Scholar
  5. 5.
    A. Boyum, Separation of leukocytes from blood and bone marrow, Scand. J. Clin. Lab. Investig. 21, supp. 97: 77 (1968).Google Scholar
  6. 6.
    K.R. Harrap and R.M. Paine, Adenosine metabolism in cultured lymphoid cells, Adv. Enz. Regln. 15: 169 (1977).CrossRefGoogle Scholar
  7. 7.
    J.F. Smyth and K.R. Harrap, Adenosine deaminase activity in leukaemia, Brit. J. Cancer 31: 544 (1975).PubMedCrossRefGoogle Scholar
  8. 8.
    R.C. Jackson, H.P. Morris and G. Weber, Adenosine deaminase and adenosine kinase in rat hepatomas and kidney tumours, Br. J. Cancer 37: 701 (1978).PubMedCrossRefGoogle Scholar
  9. 9.
    M.H.N. Tattersall and K.R. Harrap, Changes in the deoxyribo-nucleoside triphosphate pools of mouse 5178Y lymphoma cells following exposure to methotrexate or 5-fluorouracil, Cancer Res. 33: 3086 (1973).PubMedGoogle Scholar
  10. 10.
    K.R. Harrap and R.M. Paine, Use of a regulatory effector as a potential antitumour agent, Excerpta Medica, Characterisation and Treatment of Human Tumours 4: 239 (1978).Google Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • Rosanne M. Paine
    • 1
  • J. F. Smyth
    • 1
  • K. R. Harrap
    • 1
  1. 1.Institute of Cancer ResearchSutton, SurreyEngland

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