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Purine Toxicity in Human Lymphoblasts

  • Floyd F. Snyder
  • Michael S. Hershfield
  • J. Edwin Seegmiller
Chapter
Part of the Advances in Experimental Medicine and Biology book series

Abstract

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.

Keywords

Adenosine Deaminase Orotic Acid Adenosine Kinase Pyrimidine Nucleotide Severe Combine Immunodeficiency Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ADA

adenosine deaminase

AK

adenosine kinase

HPRT

hypoxanthine-guanine phosphoribosyltransferase

EHNA

erythro-9-(2-hydroxy-3-nonyl)adenine

6-MMPR

6-methylmercaptopurine ribonucleoside

APRT

adenine phosphoribosyltransferase

PP-ribose-P

phosphoribosylpyrophosphate

MEM

minimal essential medium

cAMP

adenosine 3′,5′-cyclic phosphate

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Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Floyd F. Snyder
    • 1
  • Michael S. Hershfield
    • 1
  • J. Edwin Seegmiller
    • 1
  1. 1.Department of MedicineUniversity of California, San DiegoLa JollaUSA

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