Synergistic action of 5-aza-2'-deoxycytidine and 3-deazauridine on L1210 leukemic cells and EMT6 tumor cells.

The biochemical and biological effects of the combination of 5-aza-2'-deoxycytidine (5-aza-dCyd) and 3-deazauridine (3-DU) on L1210 leukemic cells and EMT6 tumor cells were investigated. The cytotoxic action of 5-aza-dCyd and 3-DU on both L1210 and EMT6 cells in vitro was synergistic when these agents were used in combination. The combination of 5-aza-dCyd and 3-DU produced a greater inhibition of in vitro growth of L1210 and EMT6 cells than did either agent alone. The in vivo antineoplastic activity of this combination was synergistic with respect to the increased survival time of BALB/c x DBA/2 F1 mice with L1210 leukemia. 3-DU, an agent that reduces the intracellular pool size of cytosine nucleotides, stimulated the incorporation of [3H]-5-aza-dCyd into DNA of both L1210 and EMT6 cells, suggesting that the synergistic action of this combination is related to the increased incorporation of 5-aza-dCyd in the presence of 3-DU.