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Mechanisms of Damage to DNA Labeled with Electrophilic Nucleobases Induced by Ionizing or UV Radiation

Abstract

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.

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Authors (9)

  • Photo of Prof. Janusz Rak

    Janusz Rak Prof.

  • Photo of  Lidia Chomicz-Mańka

    Lidia Chomicz-Mańka

  • Photo of  Justyna Wiczk

    Justyna Wiczk

  • Photo of  Kinga Westphal

    Kinga Westphal

  • Photo of  Magdalena Zdrowowicz

    Magdalena Zdrowowicz

  • Photo of dr inż. Paweł Wityk

    Paweł Wityk dr inż.

  • Photo of  Michał Żyndul

    Michał Żyndul

  • Photo of Mgr. Samanta Makurat

    Samanta Makurat Mgr.

  • Photo of  Łukasz Golon

    Łukasz Golon

Details

Category:
Articles
Type:
artykuł w czasopiśmie wyróżnionym w JCR
Published in:
JOURNAL OF PHYSICAL CHEMISTRY B no. 119, edition 26, pages 8227 - 8238,
ISSN: 1520-6106
Language:
English
Publication year:
2015
Bibliographic description:
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:
Digital Object Identifier (open in new tab) 10.1021/acs.jpcb.5b03948
Verified by:
Gdańsk University of Technology

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