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Lookup NU author(s): Andrew Jobson,
Dr Elaine Willmore,
Dr Michael Tilby,
Professor Caroline Austin
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Purpose: Previous in vitro cleavage data showed that XR11576 and XR5944 stabilised topoisomerase I and topoisomerase II complexes on DNA in a dose-dependent fashion. However, some studies indicated a possible topoisomerase-independent mechanism of action for these drugs. Methods: Three methods, the TARDIS assay, immunoband depletion and the K+/SDS assay have been used to assess topoisomerase complex formation induced by XR11576 or XR5944 in human leukaemic K562 cells. Results: TARDIS and immunoband depletion assays demonstrated that XR11576 and XR5944 induced complex formation for both topoisomerase I and topoisomerase II (alpha and beta) in a dose- and time-dependent manner, following exposure times of 24 and 48 h at concentrations of 1 or 10 μM. The K+/SDS assay showed the formation of protein/DNA complexes after a 1 h exposure to 1 or 10 μM XR11576. Conclusion: Our data confirm that XR11576 or XR5944 can form topoisomerase complexes, after long periods of exposure. © 2008 Springer-Verlag.
Author(s): Jobson, A., Willmore, E., Tilby, M.J., Mistry, P., Charlton, P, Austin, C.
Publication type: Article
Publication status: Published
Journal: Cancer Chemotherapy and Pharmacology
Print publication date: 01/01/2008
ISSN (print): 0344-5704
ISSN (electronic): 1432-0843
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