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  • Title: Comparison of antineoplastic activity of cytosine arabinoside and 5-aza-2'-deoxycytidine against human leukemic cells of different phenotype.
    Author: Momparler RL, Onetto-Pothier N, Momparler LF.
    Journal: Leuk Res; 1990; 14(9):755-60. PubMed ID: 1700231.
    Abstract:
    A comparison of the cellular and molecular pharmacology of the deoxycytidine analogues cytosine arabinoside (Ara-C) and 5-aza-2'-deoxycytidine (5-AZA-CdR) on human myeloid (HL-60), T-cell (Molt-3) and B-cell (RPMI-8392) leukemic cell lines was investigated. Ara-C was a more potent inhibitor of growth than 5-AZA-CdR. In a colony assay, 5-AZA-CdR was a more potent cytotoxic agent than Ara-C for both the myeloid and B-cell leukemic cells, but not for the T-cell leukemic cells. The total cellular uptake of 5-AZA-CdR was greater than Ara-C for the myeloid and B-cell leukemic cells, whereas for the T-cells the uptake of the arabinosyl analogue was greater. Ara-C produced a potent inhibition of DNA synthesis, whereas no inhibition was detected with 5-AZA-CdR during a short incubation. In contrast, 5-AZA-CdR produced a potent inhibition of DNA methylation whereas Ara-C produced a slight increase in the methylation of DNA. This study shows that there are significant differences in the antineoplastic activity of Ara-C and 5-AZA-CdR against human leukemic cell lines of different phenotype and that these differences are related to differences in the metabolism of these two deoxycytidine analogues and to their effects on DNA synthesis and methylation.
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