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Uniqueness of Deoxyribonucleotide Metabolism in Human Malignant T Cell Lines

  • Dennis A. Carson
  • Jonathan Kaye
  • Steven Matsumoto
  • J. E. Seegmiller
  • Linda Thompson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 122B)

Abstract

Inherited deficiencies of the purine metabolic enzymes, adenosine deaminase (ADA) and purine nucleoside Phosphorylase (PNP) specifically impair the growth and development of the lymphoid system in human beings1,2. We have proposed that lymphospecific toxicity in these diseases might result from the selective phosphorylation and trapping by T lymphocytes of the adenosine deaminase substrate deoxyadenosine (AdR) and the purine nucleoside Phosphorylase substrate deoxyguanosine (GdR), with the subsequent formation of toxic deoxyribonucleoside triphosphates3. We further proposed that the phosphorylation was mediated by the lymphospecific enzyme deoxycytidine kinase, for which AdR and GdR are substrates, albeit poor ones4. This hypothesis was difficult to test in. vivo because of the severe lymphopenia observed in untreated enzyme deficient patients. In an effort to find a relevant in vitro model system, we therefore turned to human malignant T lymphoblasts derived from patients with T cell leukemia and a mediastinal mass. These cells are conveniently available as continuous lines and share certain antigenic and biochemical characteristics with normal primitive thymocytes5,6.

Keywords

Thymidine Kinase Adenosine Deaminase Purine Nucleoside Phosphorylase Adenosine Kinase Deoxycytidine Kinase 
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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Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • Dennis A. Carson
    • 1
    • 2
  • Jonathan Kaye
    • 1
    • 2
  • Steven Matsumoto
    • 1
    • 2
  • J. E. Seegmiller
    • 1
    • 2
  • Linda Thompson
    • 1
    • 2
  1. 1.Department of Clinical ResearchResearch Institute of Scripps ClinicLa JollaUSA
  2. 2.Department of MedicineUniversity of CaliforniaSan Diego, La JollaUSA

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