Characterization of three T-lymphoid cell lines with distinct sensitivities to deoxyadenosine plus deoxycoformycin.
Three established human T-cell lines, HPB-MLT, HPB-ALL and PEER, were characterized and tested for their sensitivity to deoxyadenosine (dAdo) plus deoxycoformycin (dCoF). Phenotypic characterizations showed that all three cell lines had receptors for peanut agglutinin (PNA) and soybean agglutinin (SBA) while HPB-MLT and HPB-ALL, but not PEER, expressed the cortical thymocyte-specific marker, CD1. The majority of HPB-MLT cells (88%) expressed only CD4 but not CD8 antigen while most HPB-ALL cells (81%) co-expressed CD8 and CD4 antigens. PEER cells were negative for both CD8 and CD4. These three T cell lines showed differential sensitivity to dAdo plus dCoF in consequent tests. dAdo or dAdo plus dCoF (1 microM) had no effect on the growth, or DNA and RNA synthesis of HPB-MLT cells while the combination of dAdo and dCoF partially inhibited cellular growth and DNA and RNA synthesis of HPB-ALL cells. Further, the growth and DNA and RNA synthesis of PEER cells were strongly inhibited by the combination of dAdo and dCoF. This high sensitivity to dAdo plus dCoF reflected an immature phenotype of PEER cells despite its expression of CD3. Flow cytometric analysis of PEER cells demonstrated disappearance of the G2/M phase cells from the cell cycle after treatment with dAdo plus dCoF. Measurements of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities in all three cell lines, however, did not establish correlations between purine metabolizing enzyme activities and the differential sensitivities to dAdo plus dCoF. In sum, we report here three T-cell lines of different phenotypes that displayed significantly different sensitivities to dAdo plus dCoF which may facilitate investigations on the mechanisms of ADA deficiency.
Duan
D S
DS
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143.
Smith
W
W
Sadée
W
W
Cowan
M J
MJ
D000243:Adenosine Deaminase / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D003839:Deoxyadenosines / Q000494:pharmacology*; D006801:Humans; D015458:Leukemia, T-Cell / Q000378:metabolism / Q000473:pathology*; D015649:Pentostatin / Q000494:pharmacology*; D010641:Phenotype; D011683:Purine-Nucleoside Phosphorylase / Q000032:analysis; D012313:RNA / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003839:Deoxyadenosines; D015649:Pentostatin; D012313:RNA; D004247:DNA; D011683:Purine-Nucleoside Phosphorylase; D000243:Adenosine Deaminase