Ecto-adenosine triphosphatase deficiency in cultured human T and null leukemic lymphocytes. A biochemical basis for thymidine sensitivity.
Cultured leukemic T and null lymphocytes are highly sensitive to growth inhibition by thymidine, as well as the other deoxynucleosides, deoxyguanosine and deoxyadenosine. By contrast, Epstein-Barr virus-transformed B lymphocytes are relatively resistant to deoxynucleosides. Growth inhibition is associated with the development of high deoxyribotriphosphate pools after exposure to the respective deoxynucleotides. We show that malignant T and null lymphocytes are deficient in ecto-ATPase activity. We show this cell surface enzyme to be of broad specificity, capable of degrading both ribotriphosphates and deoxyribotriphosphates. High levels of this ecto-enzyme are found in deoxynucleoside-resistant, Epstein-Barr virus-transformed B lymphocytes. Ecto-ATPase deficiency may represent a mechanism for increased sensitivity to deoxynucleoside growth inhibition.
D000251:Adenosine Triphosphatases / Q000172:deficiency*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D003839:Deoxyadenosines / Q000633:toxicity; D003849:Deoxyguanosine / Q000633:toxicity; D005110:Extracellular Space / Q000201:enzymology; D004854:Herpesvirus 4, Human; D006801:Humans; D007938:Leukemia / Q000201:enzymology*; D008214:Lymphocytes / Q000201:enzymology*; D013601:T-Lymphocytes / Q000201:enzymology*; D013936:Thymidine / Q000378:metabolism / Q000633:toxicity*; D013937:Thymidine Kinase / Q000378:metabolism; D013942:Thymine Nucleotides / Q000378:metabolism
D003839:Deoxyadenosines; D013942:Thymine Nucleotides; D013937:Thymidine Kinase; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D003849:Deoxyguanosine; C024157:thymidine 5'-triphosphate; D013936:Thymidine