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 language | English |
|---|---|
| Pages (from-to) | 19-24 |
| Number of pages | 6 |
| Journal | Leukemia Research |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1991 |
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Keywords
- Acute myeloid leukemia
- amsacrine
- DNA damage
- doxorubicin
- drug uptake
- flow cytometry
- topoisomerase II
ASJC Scopus subject areas
- Cancer Research
- Hematology
- Oncology
Cite this
Doxorubicin and m-AMSA induced DNA damage in blast cells from AML patients. / Limonta, Monica; Ubezio, Paolo; Catapano, Carlo V.; Conter, Valentino; Costato, Claudia; Masera, Giuseppe; Specchia, Giorgina; Liso, Vincenzo; Barbui, Tiziano; Giudici, Giovanni; D'Incalci, Maurizio.
In: Leukemia Research, Vol. 15, No. 1, 1991, p. 19-24.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Doxorubicin and m-AMSA induced DNA damage in blast cells from AML patients
AU - Limonta, Monica
AU - Ubezio, Paolo
AU - Catapano, Carlo V.
AU - Conter, Valentino
AU - Costato, Claudia
AU - Masera, Giuseppe
AU - Specchia, Giorgina
AU - Liso, Vincenzo
AU - Barbui, Tiziano
AU - Giudici, Giovanni
AU - D'Incalci, Maurizio
PY - 1991
Y1 - 1991
N2 - 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.
AB - 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.
KW - Acute myeloid leukemia
KW - amsacrine
KW - DNA damage
KW - doxorubicin
KW - drug uptake
KW - flow cytometry
KW - topoisomerase II
UR - http://www.scopus.com/inward/record.url?scp=0026020327&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026020327&partnerID=8YFLogxK
U2 - 10.1016/0145-2126(91)90139-K
DO - 10.1016/0145-2126(91)90139-K
M3 - Article
VL - 15
SP - 19
EP - 24
JO - Leukemia Research
JF - Leukemia Research
SN - 0145-2126
IS - 1
ER -