On the role of fluoro-substituted nucleosides in DNA radiosensitization for tumor radiation therapy
- 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 byGemcitabine (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.…
Author details: | Ilko BaldORCiDGND, Adrian Keller, Janina KopyraORCiD |
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DOI: | https://doi.org/10.1039/C3RA46735J |
ISSN: | 2046-2069 |
Title of parent work (English): | RSC Advances : an international journal to further the chemical sciences |
Publisher: | Royal Society of Chemistry |
Publication type: | Article |
Language: | English |
Date of first publication: | 2014/01/06 |
Publication year: | 2014 |
Release date: | 2015/03/13 |
Tag: | attachment; chemoradiation therapy; damage; drugs; gas-phase; low-energy electrons; molecular-mechanisms; resonant formation; single-strand breaks |
Volume: | 4 |
Issue: | 13 |
Number of pages: | 5 |
First page: | 6825 |
Last Page: | 6829 |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Peer review: | Referiert |
Publishing method: | Open Access |
Grantor: | RSC |
License (English): | ![]() |
External remark: | Zweitveröffentlichung als Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 167 |