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.
authors.affiliation: a Medizinische Poliklinik, University of Wuerzburg, D8700, Wuerzburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Gieseler
authors.affiliation: a Medizinische Poliklinik, University of Wuerzburg, D8700, Wuerzburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Boege
authors.affiliation: a Medizinische Poliklinik, University of Wuerzburg, D8700, Wuerzburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Biersack
authors.affiliation: a Medizinische Poliklinik, University of Wuerzburg, D8700, Wuerzburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Spohn
authors.affiliation: a Medizinische Poliklinik, University of Wuerzburg, D8700, Wuerzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Clark
authors.affiliation: a Medizinische Poliklinik, University of Wuerzburg, D8700, Wuerzburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Wilms
keywords: HL-60; Topoisomerase II; differentiation; drug-resistance; etoposide; m-amsacrine