Issue 13, 2014

On the role of fluoro-substituted nucleosides in DNA radiosensitization for tumor radiation therapy

Abstract

Gemcitabine (2′,2′-difluorocytidine) is a well-known radiosensitizer routinely applied in concomitant chemoradiotherapy. During irradiation of biological media with high-energy radiation secondary low-energy (<10 eV) electrons are produced that can directly induce chemical bond breakage in DNA by dissociative electron attachment (DEA). Here, we investigate and compare DEA to the three molecules 2′-deoxycytidine, 2′-deoxy-5-fluorocytidine, and gemcitabine. Fluorination at specific molecular sites, i.e., nucleobase or sugar moiety, is found to control electron attachment and subsequent dissociation pathways. The presence of two fluorine atoms at the sugar ring results in more efficient electron attachment to the sugar moiety and subsequent bond cleavage. For the formation of the dehydrogenated nucleobase anion, we obtain an enhancement factor of 2.8 upon fluorination of the sugar, whereas the enhancement factor is 5.5 when the nucleobase is fluorinated. The observed fragmentation reactions suggest enhanced DNA strand breakage induced by secondary electrons when gemcitabine is incorporated into DNA.

Graphical abstract: On the role of fluoro-substituted nucleosides in DNA radiosensitization for tumor radiation therapy

Article information

Article type
Paper
Submitted
15 Nov 2013
Accepted
18 Dec 2013
First published
06 Jan 2014
This article is Open Access
Creative Commons BY license

RSC Adv., 2014,4, 6825-6829

On the role of fluoro-substituted nucleosides in DNA radiosensitization for tumor radiation therapy

J. Kopyra, A. Keller and I. Bald, RSC Adv., 2014, 4, 6825 DOI: 10.1039/C3RA46735J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements