Open AccessPurinogenic immunodeficiency diseases: selective toxicity of deoxyribonucleosides for T cells.
Author(s) -
Beverly S. Mitchell,
Edwin Mejías,
Peter E. Daddona,
William N. Kelley
Publication year - 1978
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.75.10.5011
Subject(s) - deoxyadenosine , deoxyribonucleoside , deoxyguanosine , deoxyribonucleosides , adenosine deaminase , lymphoblast , adenosine deaminase inhibitor , biochemistry , purine nucleoside phosphorylase , adenosine , deoxycytidine kinase , adenosine deaminase deficiency , microbiology and biotechnology , chemistry , cell culture , biology , purine , deoxycytidine , dna , enzyme , genetics , chemotherapy , gemcitabine
Deoxyadenosine at low concentrations and in the presence of an inhibitor of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) is markedly toxic to lymphoblast cell lines of T cell origin but does not impair growth of B cell lines. Deoxyguanosine is also more toxic for T lymphoblasts. In the presence of deoxyadenosine or deoxyguanosine, elevation of the corresponding deoxyribonucleoside triphosphate (dATP or dGTP) occurs in T cell, but not in B cell, lines. The addition of deoxycytidine or dipyridamole results in lower dATP and dGTP levels and prevents deoxyribonucleoside toxicity. These findings provide a molecular basis for the immunodeficiency observed in individuals with several inborn errors of purine metabolism.