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
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 languageEnglish
JournalLeukemia and Lymphoma
Volume5
Issue number4
Pages (from-to)273-279
Number of pages7
ISSN1042-8194
DOIs
Publication statusPublished - 1991

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