Metabolism and Toxicity of 9-β-D-Arabinofuranosyladenine in Human Malignant T Cells and B Cells in Tissue Culture
In humans, a genetic deficiency of the enzyme adenosine deaminase (ADA) leads to the specific impairment of the development of the lymphoid system, with resulting immunodeficiency disease1. Recent studies have suggested that the remarkable lymphospecific toxicity seen in ADA deficiency may result from the selective accumulation of deoxyadenosine nucleotides in lymphoid tissues, particularly the thymus, which when compared to other tissues have high deoxyadenosine phosphorylating activity, and low deoxyribo-nucleotide dephosphorylating activity2–5. The dATP thereby produced inhibits DNA synthesis, probably by inhibiting ribonucleotide reductase and perhaps via other as yet undescribed mechanisms.
KeywordsAdenosine Deaminase Adenosine Kinase Deoxycytidine Kinase Inhibit Ribonucleotide Reductase Adenine Arabinoside
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