G1-phase arrest of cultured human leukemic T-cells induced by deoxyadenosine.
Cultured human T-cell leukemia lymphocytes have enhanced sensitivity to growth inhibition by deoxyadenosine. We have used flow cytometry to investigate the mechanism of deoxyadenosine toxicity in cultured T-leukemic cells. Comparative studies on deoxyadenosine-resistant Epstein-Barr virus-transformed B-lymphocyte cell lines were also performed. After exposure of T-cells to low concentrations of deoxyadenosine (3 microM), in the presence of an adenosine deaminase inhibitor (erythro-9-[3-(2-hydroxynonyl)]adenosine), accumulation of cells of cells with a G1 DNA content was demonstrated. In contrast, B-cell lines showed a similar degree of growth inhibition after exposure to 200 to 400 microM deoxyadenosine but were blocked in S phase. The T-cell G1 block was associated with a rise in the deoxyadenosine triphosphate pool, and both these phenomena were prevented by the addition of deoxycytidine. The biochemical mechanism of this G1 block induced by deoxyadenosine in T-cells is not understood.
D000248:Adenosine Kinase / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D003839:Deoxyadenosines / Q000494:pharmacology*; D003841:Deoxycytidine / Q000494:pharmacology; D003849:Deoxyguanosine / Q000494:pharmacology; D003853:Deoxyribonucleosides / Q000378:metabolism; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D013936:Thymidine / Q000494:pharmacology
D003839:Deoxyadenosines; D003853:Deoxyribonucleosides; D003841:Deoxycytidine; D000248:Adenosine Kinase; D003849:Deoxyguanosine; D013936:Thymidine; D006918:Hydroxyurea