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.

journal_name

Leuk Lymphoma

journal_title

Leukemia & lymphoma

authors

Gieseler F,Boege F,Biersack H,Spohn B,Clark M,Wilms K

doi

10.3109/10428199109068137

subject

Has Abstract

pub_date

1991-01-01 00:00:00

pages

273-9

issue

4

eissn

1042-8194

issn

1029-2403

journal_volume

5

pub_type

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