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Purine Deoxyribonucleoside Induced Hepatotoxicity in the Mouse

  • J. Renshaw
  • R. M. Paine
  • G. A. Taylor
  • K. R. Harrap
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 165)

Abstract

Although treatment of mice with the adenosine deaminase (ADA) inhibitor 2f-deoxycoformycin (dCf) in combination with 2′-deoxyadenosine (AdR) resulted in bone marrow toxicity, death was attributable to acute hepatic dysfunction.1 The toxic effects of AdR in ADA inhibited cells have been attributed to several different processes including inhibition of ribonucleotide reductase by deoxyadenosine triphosphate (dATP)2 and AdR inhibiton of S-adenosylhomocysteine (SAH) hydrolase. 3We have explored these two biochemical aspects in the livers of mice receiving AdR/dCf combinations, and report here deoxynucleoside triphosphate (dNTP) levels and preliminary measurements of perturbations in liver SAH and S-adenosylmethionine (SAM) following such treatment.

Keywords

Adenosine Deaminase Ribonucleotide Reductase Deoxynucleoside Triphosphate Bone Marrow Toxicity Potassium Bicarbonate 
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.

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References

  1. 1.
    R.M. Paine, B.J. Weston, H. McD. Clink, J. Kohn, A.M. Neville, K.G. McGhee and K.R. Harrap, Toxicity and immunosuppressive activity of binary combinations of 2′-deoxycoformycin and 2′-deoxyadenosine, Cancer Treat. Rep. 65: 259 (1981).PubMedGoogle Scholar
  2. 2.
    K.R. Harrap and R.M. Paine, Use of a regulatory effector as a potential antitumour agent, Characterisation and Treatment of Human Tumours 4: 239 (1978) Excerpta Medica.Google Scholar
  3. 3.
    M.S. Hershfield, Apparent suicide inactivation of human lymphoblast S-adenosylhomocysteine hydrolase by 2′-deoxyadenosine and adenine arabinoside, J. Biol. Chem. 254: 22 (1979).PubMedGoogle Scholar
  4. 4.
    J.F. Smyth and K.R. Harrap, Adenosine deaminase activity in leukaemia, Brit. J. Cancer 31: 544 (1975).PubMedCrossRefGoogle Scholar
  5. 5.
    M.H.N. Tattersall and K.R. Harrap, Changes in the deoxynucleoside triphosphate pools of mouse 5178Y lymphoma cells following exposure to methotrexate and 5-fluorouracil, Cancer Res. 33: 3086 (1973).PubMedGoogle Scholar
  6. 6.
    D.R. Hoffman, D.W. Marion, W.E. Cornatyer and J.A. Duerre, S-Adenosylmethionine and S-adenosylhomocysteine metabolism in isolated rat liver, J. Biol. Chem. 255: 10822 (1980).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • J. Renshaw
    • 1
  • R. M. Paine
    • 1
  • G. A. Taylor
    • 1
  • K. R. Harrap
    • 1
  1. 1.Department of Biochemical PharmacologyInstitute of Cancer ResearchSutton, SurreyEngland

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