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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.show moreshow less

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Metadaten
Author:Ilko BaldORCiDGND, Adrian Keller, Janina Kopyra
DOI:https://doi.org/10.1039/C3RA46735J
ISSN:2046-2069 (online)
Parent Title (English):RSC Advances : an international journal to further the chemical sciences
Publisher:Royal Society of Chemistry
Document Type:Article
Language:English
Date of first Publication:2014/01/06
Year of Completion: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
Pagenumber:5
First Page:6825
Last Page:6829
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
Peer Review:Referiert
Publication Way:Open Access
Grantor:RSC
Licence (English):License LogoCreative Commons - Attribution 3.0 unported
Notes extern:Zweitveröffentlichung als Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 167