Doxorubicin and m-AMSA induced DNA damage in blast cells from AML patients.
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.
Limonta
M
M
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Ubezio
P
P
Catapano
C V
CV
Conter
V
V
Costato
C
C
Masera
G
G
Specchia
G
G
Liso
V
V
Barbui
T
T
Giudici
G
G
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
D004277:DNA, Single-Stranded; D000677:Amsacrine; D004317:Doxorubicin