Purinogenic immunodeficiency diseases: selective toxicity of deoxyribonucleosides for T cells.
Deoxyadenosine at low concentrations and in the presence of an inhibitor of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) is markedly toxic to lymphoblast cell lines of T cell origin but does not impair growth of B cell lines. Deoxyguanosine is also more toxic for T lymphoblasts. In the presence of deoxyadenosine or deoxyguanosine, elevation of the corresponding deoxyribonucleoside triphosphate (dATP or dGTP) occurs in T cell, but not in B cell, lines. The addition of deoxycytidine or dipyridamole results in lower dATP and dGTP levels and prevents deoxyribonucleoside toxicity. These findings provide a molecular basis for the immunodeficiency observed in individuals with several inborn errors of purine metabolism.
D001402:B-Lymphocytes / Q000187:drug effects; D002460:Cell Line; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D003839:Deoxyadenosines / Q000633:toxicity; D003841:Deoxycytidine / Q000494:pharmacology; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D003849:Deoxyguanosine / Q000633:toxicity; D003853:Deoxyribonucleosides / Q000633:toxicity*; D004176:Dipyridamole / Q000494:pharmacology; D007153:Immunologic Deficiency Syndromes / Q000209:etiology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D003838:Deoxyadenine Nucleotides; D003839:Deoxyadenosines; D003848:Deoxyguanine Nucleotides; D003853:Deoxyribonucleosides; D003841:Deoxycytidine; D004176:Dipyridamole; D003849:Deoxyguanosine