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.…
Verfasserangaben: | Ilko BaldORCiDGND, Adrian KellerORCiD, Janina KopyraORCiD |
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DOI: | https://doi.org/10.1039/C3RA46735J |
ISSN: | 2046-2069 |
Titel des übergeordneten Werks (Englisch): | RSC Advances : an international journal to further the chemical sciences |
Verlag: | Royal Society of Chemistry |
Publikationstyp: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Erstveröffentlichung: | 06.01.2014 |
Erscheinungsjahr: | 2014 |
Datum der Freischaltung: | 13.03.2015 |
Freies Schlagwort / Tag: | attachment; chemoradiation therapy; damage; drugs; gas-phase; low-energy electrons; molecular-mechanisms; resonant formation; single-strand breaks |
Band: | 4 |
Ausgabe: | 13 |
Seitenanzahl: | 5 |
Erste Seite: | 6825 |
Letzte Seite: | 6829 |
Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Peer Review: | Referiert |
Publikationsweg: | Open Access |
Fördermittelquelle: | RSC |
Lizenz (Englisch): | Creative Commons - Namensnennung 3.0 Unported |
Externe Anmerkung: | Zweitveröffentlichung als Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 167 |