Send to

Choose Destination
Leukemia. 1996 Dec;10(12):1919-24.

Constitutive overexpression of the cytidine deaminase gene confers resistance to cytosine arabinoside in vitro.

Author information

Innere Klinik und Poliklinik (Tumorforschung), Universitätsklinikum Essen, Germany.


In search of potential therapeutic targets for enhancing the cellular detoxification of cytosine-arabinoside (ara-C), we transfected the human CDD cDNA gene into murine fibroblast cells and examined the effect of increased CDD expression on the cellular resistance to ara-C. Several cell lines were established which consistently demonstrated a 2.5-3.0-fold increase in cellular CDD activity and exhibited an up to 3.0-3.5-fold increase in the IC50 value of ara-C with regard to inhibition of cell proliferation or DNA synthesis, respectively. In the absence of ara-C, these cells maintained unaltered morphology and growth characteristics as compared with parental cells and mock-transfected controls. In addition, we examined the CDD and dCK activity in hematopoietic cells and found CD34+ hematopoietic progenitor cells to reveal a low ratio of CDD/dCK activity. Together, these data suggest that constitutive overexpression of the CDD gene correlates with increased ara-C resistance and thus may prove useful in considering attempts to attenuate ara-C-induced toxicity on hematopoietic progenitor cells.

[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center