Cytotoxic activity and mechanism of action of 5-aza-2′-deoxycytidine in human CML cells

Monica Limonta, Tina Colombo, Giovanna Damia, Carlo V. Catapano, Valentino Conter, Marco Gervasoni, Guiseppe Masera, Vincenzo Liso, Giorgina Specchia, Giovanni Giudici, Maurizio D'Incalci

Research output: Contribution to journalArticle


We investigated the cytotoxic activity and some aspects of the mode of action of 5-aza-2′-deoxycytidine (Aza-dC) in 21 primary cultures of leukemic cells freshly obtained from patients with chronic myeloid leukemia (CML) in blast crisis. The cytotoxic potency of Aza-dC was comparable or even greater than that of 1-β-d-arabinofuranosylcytosine (Ara-C) in most cases, suggesting that this drug has potential in the therapy of blast crisis of CML. Drug incorporation into DNA was evaluated by exposing leukemic cells simultaneously to 3H-Aza-dC at the concentration of 0.1 μg/ml and 14C-thymidine (TdR) used as internal standard. Incorporation of Aza-dC into DNA was detectable in all cases. In 17 samples we evaluated the DNA integrity of leukemic cells exposed to Aza-dC using alkaline elution techniques. The drug caused a detectable amount of DNA alkali labile sites (ALS). DNA-ALS increased in cells exposed to Aza-dC concentrations from 0.1 to 1 μg/ml but did not further increase at 10 μg/ml. A plateau in the levels of DNA-ALS was also seen in human K562 cells exposed to increasing concentrations of Aza-dC from 5 to 10 μg/ml, whereas in these cells Aza-dC incorporation into DNA increased with increasing Aza-dC concentrations. Therefore, DNA-ALS caused by Aza-dC are not simply the result of the chemical decomposition of azacytosine molecules incorporated into DNA, but are presumably the result of a saturable DNA repair mechanism (e.g., glycosylases) leading to formation of the apyrimidinic sites.

Original languageEnglish
Pages (from-to)977-982
Number of pages6
JournalLeukemia Research
Issue number11
Publication statusPublished - 1993


  • 5-aza-2′-deoxycytidine
  • antineoplastic agent
  • chronic myeloid leukemia
  • DNA damage

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Fingerprint Dive into the research topics of 'Cytotoxic activity and mechanism of action of 5-aza-2′-deoxycytidine in human CML cells'. Together they form a unique fingerprint.

  • Cite this

    Limonta, M., Colombo, T., Damia, G., Catapano, C. V., Conter, V., Gervasoni, M., Masera, G., Liso, V., Specchia, G., Giudici, G., & D'Incalci, M. (1993). Cytotoxic activity and mechanism of action of 5-aza-2′-deoxycytidine in human CML cells. Leukemia Research, 17(11), 977-982.