Induction of resistance to 1-beta-D-arabinofuranosylcytosine in human H9 cell line by simian immunodeficiency virus. 1995

K Yusa, and T Oh-hara, and T Tsuruo
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.

We examined drug sensitivity of human T cell acute lymphoblastic leukemia H9 cells chronically infected with simian immunodeficiency virus (SIVmac) and found that the retrovirus-infected H9 cells showed 8.2-fold resistance to 1-beta-D-arabinofuranosylcytosine (Ara-C). In the infected cells, Ara-CTP levels decreased to 20% of that found in uninfected H9 cells after 3 h incubation at Ara-C concentration of 1 microM, and 8.1-fold increase of cytidine deaminase activity was observed in the infected H9 cells. A competitive inhibitor of cytidine deaminase, 3, 4, 5, 6-tetrahydrouridine (THU), at 100 microM reversed Ara-C resistance in the infected cells. These results indicate that inducing increased cytidine deaminase activity by SIVmac infection conferred Ara-C resistance to H9 cells. An understanding of these cellular differences in drug sensitivity may aid in the development of therapeutic strategies against retrovirus-infected cells.

UI MeSH Term Description Entries
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
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
D003564 Cytidine Deaminase An enzyme that catalyzes the deamination of cytidine, forming uridine. EC 3.5.4.5. Cytidine Aminohydrolase,Aminohydrolase, Cytidine,Deaminase, Cytidine
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D005472 Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid. 5-FU,5-FU Lederle,5-FU Medac,5-Fluorouracil,5-Fluorouracil-Biosyn,5-HU Hexal,5FU,Adrucil,Carac,Efudex,Efudix,Fluoro-Uracile ICN,Fluoroplex,Fluorouracil Mononitrate,Fluorouracil Monopotassium Salt,Fluorouracil Monosodium Salt,Fluorouracil Potassium Salt,Fluorouracil-GRY,Fluorouracile Dakota,Fluorouracilo Ferrer Far,Fluoruracil,Fluracedyl,Flurodex,Haemato-FU,Neofluor,Onkofluor,Ribofluor,5 FU Lederle,5 FU Medac,5 Fluorouracil,5 Fluorouracil Biosyn,5 HU Hexal,Dakota, Fluorouracile,Fluoro Uracile ICN,Fluorouracil GRY,Haemato FU
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013767 Tetrahydrouridine An inhibitor of nucleotide metabolism. NSC-112907,NSC 112907,NSC112907
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured

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