Altered catalytic activity of and DNA cleavage by DNA topoisomerase II from human leukemic cells selected for resistance to VM-26

Biochemistry ◽  
1988 ◽  
Vol 27 (24) ◽  
pp. 8861-8869 ◽  
Author(s):  
Mary K. Danks ◽  
Carla A. Schmidt ◽  
Margaret C. Cirtain ◽  
D. Parker Suttle ◽  
William T. Beck
2008 ◽  
Vol 283 (25) ◽  
pp. 17463-17476 ◽  
Author(s):  
Felix Mueller-Planitz ◽  
Daniel Herschlag

2009 ◽  
Vol 56 (1) ◽  
Author(s):  
Krzysztof Kik ◽  
Kazimierz Studzian ◽  
Małgorzata Wasowska-Łukawska ◽  
Irena Oszczapowicz ◽  
Leszek Szmigiero

This work was undertaken to compare cytotoxicity, DNA damaging properties and effect on DNA cleavage by topoisomerase II of the anthracycline drug doxorubicin (DOX) and its two derivatives with a formamidino group containing a cyclic amine moiety such as morpholine (DOXM) or hexamethyleneimine (DOXH). The tetrazolium dye colorimetric assay was used to determine the cytotoxic activity of anthracyclines toward L1210 leukemia cells. DNA damage was measured by alkaline elution technique. The effect of anthracyclines on DNA cleavage was studied in a cell-free system containing supercoiled pBR322 DNA and purified human topoisomerase II. The cytotoxicity data and the results of studies on the mechanism of DNA break formation by anthracyclines at the cellular level and in the cell-free system showed that the presence of the formamidino group in the doxorubicin molecule reduced its ability to stimulate DNA cleavage by DNA topoisomerase II. DNA topoisomerase II is not a primary cellular target for DOXM or DOXH. An advantageous feature of formamidinoanthracyclines is their mechanism of cytotoxic action which is not related to the inhibition of DNA topoisomerase II. Therefore this class of anthracyclines seems to be a good source for selection of an anticancer drug directed toward cancer cells with the developed multidrug resistance attributed to the presence of altered DNA topoisomerase II.


1996 ◽  
Vol 52 (11) ◽  
pp. 1675-1685 ◽  
Author(s):  
Katherine L. Marsh ◽  
Elaine Willmore ◽  
Stella Tinelli ◽  
Mariagrazia Cornarotti ◽  
Emma L. Meczes ◽  
...  

1988 ◽  
Vol 37 (11) ◽  
pp. 2145-2149 ◽  
Author(s):  
Jean-Yves Charcosset ◽  
Jean-Marie Saucier ◽  
Alain Jacquemin-Sablon

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