Nuclear topoisomerase II activity changes during HL-60 leukemic cell differentiation: Alterations in drug sensitivity and ph dependency

Frank Gieseler; Fritz Boege; Harald Biersack; Birgit Spohn; Michael Clark; Klaus Wilms

doi:10.3109/10428199109068137

Nuclear topoisomerase II activity changes during HL-60 leukemic cell differentiation: Alterations in drug sensitivity and ph dependency

Frank Gieseler^*, Fritz Boege, Harald Biersack, Birgit Spohn, Michael Clark, Klaus Wilms

^*Corresponding author for this work

Department of Internal Medicine I

University of Würzburg

6 Citations (Scopus)

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.

Original language	English
Journal	Leukemia and Lymphoma
Volume	5
Issue number	4
Pages (from-to)	273-279
Number of pages	7
ISSN	1042-8194
DOIs	https://doi.org/10.3109/10428199109068137
Publication status	Published - 1991

Funding

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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@article{1882d754b7e54ee58d7ba7d4ac93d5d0,

title = "Nuclear topoisomerase II activity changes during HL-60 leukemic cell differentiation: Alterations in drug sensitivity and ph dependency",

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.",

author = "Frank Gieseler and Fritz Boege and Harald Biersack and Birgit Spohn and Michael Clark and Klaus Wilms",

note = "Funding Information: 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.",

year = "1991",

doi = "10.3109/10428199109068137",

language = "English",

volume = "5",

pages = "273--279",

journal = "Leukemia and Lymphoma",

issn = "1042-8194",

publisher = "Taylor and Francis Ltd.",

number = "4",

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TY - JOUR

T1 - Nuclear topoisomerase II activity changes during HL-60 leukemic cell differentiation: Alterations in drug sensitivity and ph dependency

AU - Gieseler, Frank

AU - Boege, Fritz

AU - Biersack, Harald

AU - Spohn, Birgit

AU - Clark, Michael

AU - Wilms, Klaus

N1 - Funding Information: 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.

PY - 1991

Y1 - 1991

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/0025942129

U2 - 10.3109/10428199109068137

DO - 10.3109/10428199109068137

M3 - Journal articles

AN - SCOPUS:0025942129

SN - 1042-8194

VL - 5

SP - 273

EP - 279

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

IS - 4

ER -

Nuclear topoisomerase II activity changes during HL-60 leukemic cell differentiation: Alterations in drug sensitivity and ph dependency

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