Cell Cycle Independent Lymphocytotoxicity of 2-Chlorodeoxyadenosine
Deoxyadenosine and its nucleotides have been implicated in the pathogenesis of the immunodeficient state associated with an inherited deficiency of adenosine deaminase (ADA) (1,2), In ADA deficient patients, T lymphocytes may selectively phosphorylate deoxyadenosine released by other tissues. Both dividing and resting T cells have abundant deoxyadenosine phosphorylating activity, mediated primarily by deoxycytidine kinase, but minimal deoxynucleotide dephosphorylating activity, mediated by cytoplasmic deoxynucleotidase (3,4). For this reason, normal and malignant T lymphocytes exposed to micromolar concentrations of deoxyadenosine, in the presence of an ADA inhibitor, progressively accumulate dATP until cell death ultimately ensues (5,6).
KeywordsAdenosine Deaminase Lymphoblastoid Cell Line Cytosine Arabinoside Severe Combine Immunodeficiency Purine Nucleoside Phosphorylase
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