Mechanism of synergistic cell killing by hydroxyurea and cytosine arabinoside. 1985

M Tanaka, and K Kimura, and S Yoshida

Synergistic cell killing of human lymphoblastic leukemia cell line, CCRF-CEM, occurred when hydroxyurea (HU) was administered before 1-beta-D-arabinofuranosylcytosine (ara-C). At the optimal dose of HU (1mM), the ara-CTP concentration increased 4-fold and the intracellular accumulation of ara-C increased 4-fold, while the dCTP concentration decreased by more than 50%. Increased intracellular accumulation of ara-C after HU treatment was also observed in human acute myelogenous leukemic cells in circulating blood. Therefore, the synergistic cell kill of HU and ara-C may be the consequence of greater inhibition of DNA polymerase by the increased level of ara-CTP in the presence of the decreased concentration of the natural substrate of this enzyme, dCTP. This synergism was not due to an increased incorporation of ara-C into DNA since the treatment of cells with HU did not enhance the ara-C incorporation into DNA but rather suppressed it.

UI MeSH Term Description Entries
D007945 Leukemia, Lymphoid Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts. Leukemia, Lymphocytic,Lymphocytic Leukemia,Lymphoid Leukemia,Leukemias, Lymphocytic,Leukemias, Lymphoid,Lymphocytic Leukemias,Lymphoid Leukemias
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003561 Cytarabine A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472) Ara-C,Arabinofuranosylcytosine,Arabinosylcytosine,Cytosine Arabinoside,Aracytidine,Aracytine,Cytarabine Hydrochloride,Cytonal,Cytosar,Cytosar-U,beta-Ara C,Ara C,Arabinoside, Cytosine,Cytosar U,beta Ara C
D003845 Deoxycytosine Nucleotides Cytosine nucleotides which contain deoxyribose as the sugar moiety. Deoxycytidine Phosphates,Nucleotides, Deoxycytosine,Phosphates, Deoxycytidine
D003854 Deoxyribonucleotides A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group. Deoxyribonucleotide
D004273 DNA, Neoplasm DNA present in neoplastic tissue. Neoplasm DNA
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006918 Hydroxyurea An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. Hydroxycarbamid,Hydrea,Oncocarbide

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