Mechanisms of Damage to DNA Labeled with Electrophilic Nucleobases Induced by Ionizing or UV Radiation
Abstrakt
Hypoxia—a hallmark of solid tumors—makes hypoxic cells radioresistant. On the other hand, DNA, the main target of anticancer therapy, is not sensitive to the near UV photons and hydrated electrons, one of the major products of water radiolysis under hypoxic conditions. A possible way to overcome these obstacles to the efficient radio- and photodynamic therapy of cancer is to sensitize the cellular DNA to electrons and/or ultraviolet radiation. While incorporated into genomic DNA, modified nucleosides, 5-bromo-2′-deoxyuridine in particular, sensitize cells to both near-ultraviolet photons and γ rays. It is believed that, in both sensitization modes, the reactive nucleobase radical is formed as a primary product which swiftly stabilizes, leading to serious DNA damage, like strand breaks or cross-links. However, despite the apparent similarity, such radio- and photosensitization of DNA seems to be ruled by fundamentally different mechanisms. In this review, we demonstrate that the most important factors deciding on radiodamage to the labeled DNA are (i) the electron affinity (EA) of modified nucleoside (mNZ), (ii) the local surroundings of the label that significantly influences the EA of mNZ, and (iii) the strength of the chemical bond holding together the substituent and a nucleobase. On the other hand, we show that the UV damage to sensitized DNA is governed by long-range photoinduced electron transfer, the efficiency of which is controlled by local DNA sequences. A critical review of the literature mechanisms concerning both types of damage to the labeled biopolymer is presented. Ultimately, the perspectives of studies on DNA sensitization in the context of cancer therapy are discussed.
Cytowania
-
7 5
CrossRef
-
0
Web of Science
-
7 2
Scopus
Autorzy (9)
Cytuj jako
Pełna treść
pełna treść publikacji nie jest dostępna w portalu
Słowa kluczowe
Informacje szczegółowe
- Kategoria:
- Publikacja w czasopiśmie
- Typ:
- artykuł w czasopiśmie wyróżnionym w JCR
- Opublikowano w:
-
JOURNAL OF PHYSICAL CHEMISTRY B
nr 119,
wydanie 26,
strony 8227 - 8238,
ISSN: 1520-6106 - Język:
- angielski
- Rok wydania:
- 2015
- Opis bibliograficzny:
- Rak J., Chomicz-Mańka L., Wiczk J., Westphal K., Zdrowowicz M., Wityk P., Żyndul M., Makurat S., Golon Ł.: Mechanisms of Damage to DNA Labeled with Electrophilic Nucleobases Induced by Ionizing or UV Radiation// JOURNAL OF PHYSICAL CHEMISTRY B. -Vol. 119, iss. 26 (2015), s.8227-8238
- DOI:
- Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1021/acs.jpcb.5b03948
- Weryfikacja:
- Politechnika Gdańska
wyświetlono 160 razy
Publikacje, które mogą cię zainteresować
Targeting shelterin proteins for cancer therapy.
- W. Brankiewicz-Kopcinska,
- A. Kallingal,
- R. Krzemieniecki
- + 1 autorów
Hydroperoxyl radical and formic acid formation from common DNA stabilizers upon low energy electron attachment
- A. Ribar,
- S. Huber,
- M. Śmiałek-Telega
- + 5 autorów
H2O˙+ and OH+ reactivity versus furan: experimental low energy absolute cross sections for modeling radiation damage
- D. Ascenzi,
- E. Erdmann,
- P. Bolognesi
- + 9 autorów