Modulation of the effect of 1-beta-D-arabinofuranosylcytosine based on changes of cytidine deaminase activity in HL60 cells.

The effect of changes in cytidine deaminase activity on the growth inhibitory effect of 1-beta-D-arabinofuranosylcytosine (Ara-C) has been investigated in the human promyelocytic cell line, HL60. 1,25 Dihydroxy vitamin D3 (vit. D3), which is an inducer of differentiation, caused an increase of cytidine deaminase in HL60 cells simultaneous with an inhibition of the effect of Ara-C. On the other hand, retinoic acid, which also induces differentiation had no influence on either the activity of cytidine deaminase or the effect of Ara-C. An atoxic inhibitor of cytidine deaminase tetrahydrouridine, THU, enhanced the effect of Ara-C. THU also enhanced the effect of Ara-C, even if the Ara-C effect was inhibited by deoxycytidine. These results show that it is possible to modulate the effect of Ara-C by changing the activity of cytidine deaminase. Furthermore, changes in the activity of cytidine deaminase and the effect on the Ara-C growth inhibition vary dependent on the differentiating inducer used.