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ABSTRACT We examined the cellular effects of topo II inhibitors in two human myeloid cell lines, HL-60 and KG-1 cells, with the purpose of finding molecular markers for the sensitivity of

leukemia cells to topo II inhibitors. These cell lines are widely used, well characterized and they differ in their sensitivities to topo II inhibitors. Despite the fact that HL-60 cells are

p53-negative, they are much more sensitive than KG-1 cells. Three different topo II inhibitors with distinct molecular ways of action have been used. Daunorubicin and aclarubicin are DNA

intercalators that secondarily interact with topo II; etoposide, on the other hand, directly binds to the enzyme. In contrast to daunorubicin, which induces protein-associated DNA

double-strand breaks due to the blockage of topo II action, aclarubicin inhibits the access of DNA by topo II. No correlation could be established between the drug-induced DNA damage and

apoptosis. In fact, the amount and pattern of DNA damage examined with the ‘comet assay’ was characteristic for each drug in both cell lines. The DNA binding of daunorubicin was slightly

higher in HL-60 cells, but there was no notable variance between the cell lines for aclarubicin. The most striking difference could be found for the nuclear topo II activity, which was about

half in KG-1 cells and, additionally, less than 1% of the nuclear topo II activity was bound to the DNA in KG-1 cells when compared to HL-60 cells. This fraction of topo II interacts with

the inhibitors; subsequently these findings might well explain the variance in the cellular sensitivity. Additional factors are alterations of the apoptotic pathways, eg loss of p53 in HL-60

cells. Although we found no differences in the quantity of DNA damage between the cell lines after drug treatment, the quality of DNA damage appeared to be distinct for each topo II

inhibitor. The morphological appearance of the comet tails after treatment was characteristic for each drug. Further studies are necessary to decide whether these _in vitro_ data are

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Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS DNA-PK INHIBITOR PEPOSERTIB ENHANCES P53-DEPENDENT CYTOTOXICITY OF DNA DOUBLE-STRAND BREAK INDUCING THERAPY IN

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AUTHORS AND AFFILIATIONS * University Hospital, Klinik für Allgemeine Innere Medizin, Kiel, Germany F Gieseler & M Clark * University Hospital, Medizinische Poliklinik, Würzburg, Germany

E Bauer & S Valsamas * University Hospital, Klinikum Grosshadern, Munich, Germany V Nuessler Authors * F Gieseler View author publications You can also search for this author inPubMed 

Google Scholar * E Bauer View author publications You can also search for this author inPubMed Google Scholar * V Nuessler View author publications You can also search for this author

inPubMed Google Scholar * M Clark View author publications You can also search for this author inPubMed Google Scholar * S Valsamas View author publications You can also search for this

author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Gieseler, F., Bauer, E., Nuessler, V. _et al._ Molecular effects of

topoisomerase II inhibitors in AML cell lines: correlation of apoptosis with topoisomerase II activity but not with DNA damage. _Leukemia_ 13, 1859–1863 (1999).

https://doi.org/10.1038/sj.leu.2401570 Download citation * Received: 12 August 1998 * Accepted: 12 July 1999 * Published: 03 November 1999 * Issue Date: 01 November 1999 * DOI:

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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * chemotherapy, leukemia, topoisomerase, DNA damage