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, Janina KopyraORCiD, Adrian KellerORCiD |
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URN: | urn:nbn:de:kobv:517-opus4-73412 |
Schriftenreihe (Bandnummer): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (paper 167) |
Publikationstyp: | Postprint |
Sprache: | Englisch |
Datum der Erstveröffentlichung: | 06.01.2014 |
Erscheinungsjahr: | 2014 |
Veröffentlichende Institution: | Universität Potsdam |
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 |
Seitenanzahl: | 5 |
Erste Seite: | 6825 |
Letzte Seite: | 6829 |
Quelle: | RSC Advances, 13 (2014) 4, S. 6825–6829. - DOI 10.1039/C3RA46735J |
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 |
Lizenz (Englisch): | Creative Commons - Namensnennung 3.0 Unported |
Externe Anmerkung: | Bibliographieeintrag der Originalveröffentlichung/Quelle |