Possible Role for 5′-Nucleotidase in Deoxyadenosine Selective Toxicity to Cultured Human Lymphoblasts

  • Robert L. Wortmann
  • Beverly S. Mitchell
  • N. Lawrence Edwards
  • Irving H. Fox
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 122B)

Abstract

Adenosine deaminase deficiency and purine nucleoside Phosphorylase deficiency are relatively specific for causing a disorder of immune function. Several in vitro observations provide clues concerning the basis for this specificity. The addition of deoxyadenosine reduces the response of peripheral blood lymphocytes to mitogen stimulation when adenosine deaminase is inhibi ted1,2. The combination of deoxyadenosine and adenosine deaminase inhibition is also cytotoxic to T-lymphoblasts but not B-lymphoblasts3–5. Deoxyadenosine mediated cytoxicity in T-lymphoblasts is accompanied by increased concentrations of dATP.

Keywords

Toxicity Adenosine Purine Nucleoside Triphosphate 

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References

  1. 1.
    H. A. Simmonds, G. S. Panay, and F. Corrigali, A role for purine metabolism in the immune response: Adenosine deaminase activity and deoxyadenosine catabolism, Lancet 1:60 (1978).PubMedCrossRefGoogle Scholar
  2. 2.
    D. A. Carson, J. Kaye, and J. E. Seegmiller, Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside Phosphorylase deficiency: Possible role of nucleoside kinase(s), Proc. Natl. Acad. Sci. USA 74:5677 (1977).PubMedCrossRefGoogle Scholar
  3. 3.
    B. S. Mitchell, E. Mejias, P. E. Daddona, and W. N. Kelley, Purinogenic immunodeficiency diseases: Selective toxicity of deoxyribonucleosides for T-cells, Proc. Natl. Acad. Sci. USA 75:5011 (1978).PubMedCrossRefGoogle Scholar
  4. 4.
    D. A. Carson, J. Kaye, and J. E. Seegmiller, Differential sensitivity of human leukemic T-cell lines and B-cell lines to growth inhibition by deoxyadenosine, J. Immunol. 121: 1726 (1978).PubMedGoogle Scholar
  5. 5.
    E. W. Gelfand, J. L. Lee, and H. M. Dosch, Selective toxicity of purine deoxynucleosides for human lymphocyte growth and function, Proc. Natl. Acad. Sci. USA 76:1998 (1979).PubMedCrossRefGoogle Scholar
  6. 6.
    R. L. Wortmann, B. S. Mitchell, N. L. Edwards, and I. H. Fox, Biochemical basis for differential deoxyadenosine toxicity to T- and B-lymphoblasts: A role for 5′-nucleotidase. Proc. Natl. Acad. Sci. USA 76:2434 (1979).PubMedCrossRefGoogle Scholar
  7. 7.
    D. A. Carson, J. Kaye, S. Matsumoto, J. E. Seegmiller, and L. Thompson, Biochemical basis for the enhanced toxicity of deoxyribonucleosides toward malignant human T-cell lines. Proc. Natl. Acad. Sci. USA 76:2430 (1979).PubMedCrossRefGoogle Scholar
  8. 8.
    N. L. Edwards, E. W. Gelfand, L. Burk, H. M. Dosch, and I. H. Fox, Distribution of 5′-nucleotidase in human lymphoid tissue. Proc. Natl. Acad. Sci. USA 76:(In Press) (1979).Google Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • Robert L. Wortmann
    • 1
  • Beverly S. Mitchell
    • 1
  • N. Lawrence Edwards
    • 1
  • Irving H. Fox
    • 1
  1. 1.Human Purine Research Center, Departments of Internal Medicine and Biological ChemistryUniversity of MichiganAnn ArborUSA

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