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  • Title: Constitutive overexpression of the cytidine deaminase gene confers resistance to cytosine arabinoside in vitro.
    Author: Schröder JK, Kirch C, Flasshove M, Kalweit H, Seidelmann M, Hilger R, Seeber S, Schütte J.
    Journal: Leukemia; 1996 Dec; 10(12):1919-24. PubMed ID: 8946931.
    Abstract:
    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.
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