Doxorubicin and m-AMSA induced DNA damage in blast cells from AML patients

Monica Limonta, Paolo Ubezio, Carlo V. Catapano, Valentino Conter, Claudia Costato, Giuseppe Masera, Giorgina Specchia, Vincenzo Liso, Tiziano Barbui, Giovanni Giudici, Maurizio D'Incalci

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated m-AMSA or doxorubicin (Dx) induced DNA single-strand breaks (DNA-SSB) in myeloid leukemia cells obtained from 8 adult patients suffering from AML. Highly purified AML cells were stimulated to proliferate with the addition of the appropriate growth factor (GCT) and exposed to different concentrations of m-AMSA or Dx for 1 or 4 h, respectively. DNA-SSB were determined by alkaline elution techniques. Either the kinetics or the amounts of DNA-SSB caused by both topoisomerase II inhibitors were variable among different cases. By increasing m-AMSA concentrations there was a concomitant increase in DNA-SSB up to a plateau at the highest concentrations. Dx induced DNA-SSB followed a bell shape curve with a decrease in the number of breaks at the highest concentrations that was evident in most cases. The interindividual variability of Dx-induced DNA-SSB was not correlated with intracellular Dx concentrations as assessed by flow cytometry. No correlation was evident between the amount of DNA breaks induced by m-AMSA and that induced by Dx. These data suggest that AML cells derived from different patients are not necessarily cross-sensitive or cross-resistant to topoisomerase II inhibitors with different chemical structures such as amsacrine or anthracyclines.

Original languageEnglish
Pages (from-to)19-24
Number of pages6
JournalLeukemia Research
Volume15
Issue number1
DOIs
Publication statusPublished - 1991

Keywords

  • Acute myeloid leukemia
  • amsacrine
  • DNA damage
  • doxorubicin
  • drug uptake
  • flow cytometry
  • topoisomerase II

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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