Purine Toxicity in Human Lymphoblasts
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The selective toxicity of adenosine to dividing lymphoid cells is considered a possible basis for a type of severe combined immunodeficiency disease in which there is absence of adenosine deaminase (ADA)1 activity, the enzyme which converts adenosine to inosine. Treatment of lymphoid cells with adenosine has been reported to lower intracellular pyrimidine nucleotide concentrations (1,2) and to transiently increase adenosine 3′,5′-cyclic phosphate (cAMP) concentration (3,4). We have recently shown that depletion of intracellular phosphoribosylpyrophosphate (PP-ribose-P) concentration in cultured human lymphoblasts is responsible for the decrease in concentration of nucleotides dependent on PP-ribose-P for their synthesis (5). It is not known which of these several effects are mediated by adenosine directly or by phosphorylated products of adenosine. We now present evidence that adenosine’s toxicity may not require its phosphorylation and does not depend upon change in cAMP concentration.
KeywordsAdenosine Deaminase Orotic Acid Adenosine Kinase Pyrimidine Nucleotide Severe Combine Immunodeficiency Disease
minimal essential medium
adenosine 3′,5′-cyclic phosphate
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