Induction of cytidine deaminase in HL-60 myeloid leukemic cells by 5-aza-2'-deoxycytidine.

5-Aza-2'-deoxycytidine (5-AZA-CdR), a potent inhibitor of DNA methylation and an active antileukemic agent, produced an induction of cytidine deaminase activity in human HL-60 myeloid leukemic cells. This increase in enzyme activity correlated with the induction of differentiation of the HL-60 leukemic cells as shown by an increase in nitroblue tetrazolium reduction, loss of clonogenicity and decrease in DNA synthesis. The concentration of 5-AZA-CdR that produced these effects was in the range of 0.1-1.0 microM. The increase in cytidine deaminase activity became apparent starting at 48 h from the start of the 5-AZA-CdR treatment and at 72 h was about 6-fold greater than the non-treated cell. Since cytidine deaminase is the major enzyme involved in the catabolism of cytosine nucleoside analogues, these results may be relevant in the evaluation of the clinical response of leukemic patients treated with 5-AZA-CdR.