Zitieren Sie bitte immer diesen URN: urn:nbn:de:kobv:b43-302872
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 fragmentationGemcitabine (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.…
Autor*innen: | J. Kopyra, A. Keller, Ilko Bald |
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Dokumenttyp: | Zeitschriftenartikel |
Veröffentlichungsform: | Verlagsliteratur |
Sprache: | Englisch |
Titel des übergeordneten Werkes (Englisch): | RSC Advances |
Jahr der Erstveröffentlichung: | 2014 |
Veröffentlichende Institution: | Bundesanstalt für Materialforschung und -prüfung (BAM) |
Verlag: | RSC Publishing |
Verlagsort: | London |
Jahrgang/Band: | 4 |
Ausgabe/Heft: | 13 |
Erste Seite: | 6825 |
Letzte Seite: | 6829 |
Freie Schlagwörter: | DNA radiation damage; DNA radiosensitizer; Dissociative electron attachment; Gemcitabine; Tumor radiation therapy |
DOI: | 10.1039/c3ra46735j |
URN: | urn:nbn:de:kobv:b43-302872 |
ISSN: | 2046-2069 |
Verfügbarkeit des Dokuments: | Datei für die Öffentlichkeit verfügbar ("Open Access") |
Lizenz (Deutsch): | Creative Commons - Namensnennung |
Datum der Freischaltung: | 20.02.2016 |
Referierte Publikation: | Ja |
Datum der Eintragung als referierte Publikation: | 03.03.2014 |
Schriftenreihen ohne Nummerierung: | Wissenschaftliche Artikel der BAM |