5-AZA-2′-Deoxycytidine Synergistic action with Thymidine on Leukemic Cells and Interaction of 5-AZA-dCMP with dCMP Deaminase
5-Aza-2′-deoxycytidine (5-AZA-CdR) is a potent antileukemic agent whose inhibitory effects are blocked by deoxycytidine (1-3). In order to be active, 5-AZA-CdR must first be phosphorylated by the enzyme deoxycytidine kinase (4). Leukemic cells deficient in the enzyme are resistant to 5-AZA-CdR (5). The lethal action of 5-AZA-CdR is related to its incorporation into DNA (6,7). The incorporation of 5-azacytosine analogs into DNA has been shown to induce the expression of differentiated phenotypes (8). This induction of differentiation by 5-AZA-CdR appears to be related to the inhibition of DNA methylation produced by these analogs (8, 9).
KeywordsPool Size Ribonucleotide Reductase Cytosine Arabinoside L1210 Leukemic Cell Human Promyelocytic Leukemia Cell Line
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