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Purinogenic Immunodeficiency Diseases: DIFFERENTIAL EFFECTS OF DEOXYADENOSINE AND DEOXYGUANOSINE ON DNA SYNTHESIS IN HUMAN T LYMPHOBLASTS
James M. Wilson, … , Peter E. Daddona, William N. Kelley
James M. Wilson, … , Peter E. Daddona, William N. Kelley
Published November 1, 1979
Citation Information: J Clin Invest. 1979;64(5):1475-1484. https://doi.org/10.1172/JCI109606.
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Purinogenic Immunodeficiency Diseases: DIFFERENTIAL EFFECTS OF DEOXYADENOSINE AND DEOXYGUANOSINE ON DNA SYNTHESIS IN HUMAN T LYMPHOBLASTS

Abstract

Deoxyadenosine and deoxyguanosine are toxic to human lymphoid cells in culture and have been implicated in the pathogenesis of the immunodeficiency states associated with adenosine deaminase and purine nucleoside phosphorylase deficiency, respectively. We have studied the relative incorporation of several labeled nucleosides into DNA and into nucleotide pools to further elucidate the mechanism of deoxyribonucleoside toxicity. In the presence of an inhibitor of adenosine deaminase [erythro-9-(2-hydroxy-3-nonyl)adenine [EHNA], 5 μM], deoxyadenosine (1-50 μM) progressively decreased the incorporation of thymidine, uridine, and deoxyuridine into DNA, but did not affect uridine incorporation into RNA. This decrease in DNA synthesis was associated with increasing dATP and decreasing dCTP pools. Likewise, incubation of cells with deoxyguanosine caused an elevation of dGTP, depletion of dCTP, and inhibition of DNA synthesis.

Authors

James M. Wilson, Beverly S. Mitchell, Peter E. Daddona, William N. Kelley

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