title: Doxorubicin and m-AMSA induced DNA damage in blast cells from AML patients.
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.
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Limonta
authors.forename: P
authors.initials: P
authors.lastname: Ubezio
authors.forename: C V
authors.initials: CV
authors.lastname: Catapano
authors.forename: V
authors.initials: V
authors.lastname: Conter
authors.forename: C
authors.initials: C
authors.lastname: Costato
authors.forename: G
authors.initials: G
authors.lastname: Masera
authors.forename: G
authors.initials: G
authors.lastname: Specchia
authors.forename: V
authors.initials: V
authors.lastname: Liso
authors.forename: T
authors.initials: T
authors.lastname: Barbui
authors.forename: G
authors.initials: G
authors.lastname: Giudici
mesh_terms: D000328:Adult; D000368:Aged; D000677:Amsacrine / Q000494:pharmacology*; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged
chemical_list: D004277:DNA, Single-Stranded; D000677:Amsacrine; D004317:Doxorubicin