Influence of gemcitabine (2 ',2 '-difluorodeoxycytidine) and 2-chlorodeoxyadenosine on growth of normal and leukemic cells in vitro

The aim of the study was to investigate the influence of gemcitabine (2',2' -difluorodeoxycytidine, dFdC) used alone and in combination with 2-chlorode oxyadenosine (2-CdA) on the colony growth of normal granulocyte-macrophage progenitor cells (CFU-GM) from 15 hematologically healthy donors as well as on CFU-GM from 15 chronic myelogenous leukemia (CML) patients in semisolid cultures in vitro. dFdC and 2-CdA were used either separately or in the fo llowing combinations of concentrations: (1) 0.25 nM of dFdC and 2.5 nM of 2 -CdA; (2) 0.5 nM of dFdC and 5 nM of 2-CdA; (3) 1 nM of dFdC and 10 nM of 2 -CdA; (4) 2 nM of dFdC and 20 nM of 2-CdA. We observed that both dFdC and 2 -CdA used separately inhibited the growth of colonies formed by normal and CML CFU-GM cells in a dose-dependent manner. Moreover, the combined therapy with dFdC and 2-CdA caused statistically significant inhibition of the col ony growth in both normal and CML CFU-GM cultures. In addition, the inhibit ion of CML CFU-GM colony formation was greater and statistically significan t in the case of the combined therapy using higher concentrations of these drugs as compared with inhibition of the growth of normal CFU-GM colonies. These observations were the basis for the evaluation of the interaction typ e between dFdC and 2-CdA. We have shown that dFdC used in a combination wit h 2-CdA acts in an additive way on normal and CML CFU-GM cells.