Abstract
We have studied the effect of dimethyl-sulfoxide(DMSO)-induced granulocytic differentiation on the sensitivity of HL-60 cells to various cytotoxic topoisomerase II inhibitors: (i) undifferentiated HL-60 cells are highly sensitive to etoposide, while differentiated HL-60 cells are 700-1000 fold resistant to etoposide, (ii) undifferentiated HL-60 are 50-100 fold resistant against 4-(9-acridinylamino)methanesulfon-m-anisidide (mAMSA) when compared to the differentiated HL-60 cells, (iii) the addition of mAMSA to the medium inhibits granulocytic differentiation of HL-60 cells. This change in resistance pattern is probably due to an alteration of topoisomerases since distinctive iso-activites of topoisomerase can be discriminated on the basis of the pH profile, which alters markedly during differentiation. In an etoposide-resistant HL-60 cell line we found a reduced topoisomerase activity at pH 7.8/7.9. This topoisomerase iso-activity is obviously involved in etoposide cytotoxicity.
| Originalsprache | Englisch |
|---|---|
| Zeitschrift | Leukemia and Lymphoma |
| Jahrgang | 5 |
| Ausgabenummer | 4 |
| Seiten (von - bis) | 273-279 |
| Seitenumfang | 7 |
| ISSN | 1042-8194 |
| DOIs | |
| Publikationsstatus | Veröffentlicht - 1991 |
Fördermittel
Acknowledgements We thank Cyanamid-Lederie GmBH, Wol-fratshausen, FRG, for providing the Luminescence Spectrometer (LS-50, Perkin Elmer, Ueberlingen, FRG) which made this work possible. This work was supported by Deutsche Forschungsge-meinschaft, SFB 172, C9 and the Wilhelm Sander-Stiftung, grant 90.038.1.
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SDG 3 – Gesundheit und Wohlergehen
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