ORBi: Coucke Philippe - Simultaneous alteration of de novo and salvage pathway to the deoxynucleoside thriphosphate pool by (E)-2'-deoxy-(fluoromethylene)cytidine (FMDC) and zidovudine (AZT) results in increased radiosensitivity in vitro.

Reference : Simultaneous alteration of de novo and salvage pathway to the deoxynucleoside thriphosph...


	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Hematology Human health sciences : Oncology
	To cite this reference:	http://hdl.handle.net/2268/5920

Title :	Simultaneous alteration of de novo and salvage pathway to the deoxynucleoside thriphosphate pool by (E)-2'-deoxy-(fluoromethylene)cytidine (FMDC) and zidovudine (AZT) results in increased radiosensitivity in vitro.
Language :	English
Author, co-author :	Coucke, Philippe [Centre Hospitalier Universitaire de Liège - CHU > Radiothérapie >]
	Cottin, Eliane [ > > ]
	Laurent, A. [ > > ]
	Decosterd, A. [ > > ]
Publication date :	2007
Journal title :	Acta Oncologica
Publisher :	Taylor & Francis
Volume :	46
Pages :	612-620
Audience :	International
ISSN :	0284-186X
e-ISSN :	1651-226X
City :	Oslo
Country :	Norway
Keywords :	[en] radiotherapy ; AZT ; FMdC
	[fr] cancer
Abstract :	[en] Abstract To test whether a thymidine analog zidovudine (=AZT), is able to modify the radiosensitizing effects of (E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC). A human colon cancer cell line Widr was exposed for 48 hours prior to irradiation to FMdC. Zidovudine was added at various concentrations immediately before irradiation. We measured cell survival and the effect of FMdC, AZT and FMdC + AZT on deoxynucleotide triphosphate pool. FMdC results in a significant increase of radiosensitivity. The enhancement ratios (ER =surviving fraction irradiated cells/surviving fraction drug treated and irradiated cells), obtained by FMdC or AZT alone are significantly increased by the combination of both compounds. Adding FMdC to AZT yields enhancement ratios ranging from 1.25 to 2.26. FMdC reduces dATP significantly, with a corresponding increase of TTP, dCTP and dGTP. This increase of TTP, dCTP and dGTP is abolished with the addition of AZT. Adding AZT to FMdC results in a significant increase of the radiosensitizing effect of FMdC. This combination appears to reduce the reactive enhancement of TTP, dCTP and dGTP induced by FMdC while it does not affect the inhibitory effect on dATP.
Target :	Researchers ; Professionals
Permalink :	http://hdl.handle.net/2268/5920

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