One-electron oxidation reactions of purine and pyrimidine bases in cellular DNA

Jean Cadet, J. Richard Wagner, Vladimir Shafirovich, Nicholas Geacintov

Research output: Contribution to journalArticle

Abstract

Purpose: The aim of this survey is to critically review the available information on one-electron oxidation reactions of nucleobases in cellular DNA with emphasis on damage induced through the transient generation of purine and pyrimidine radical cations. Since the indirect effect of ionizing radiation mediated by hydroxyl radical is predominant in cells, efforts have been made to selectively ionize bases using suitable one-electron oxidants that consist among others of high intensity UVC laser pulses. Thus, the main oxidation product in cellular DNA was found to be 8-oxo-7,8-dihydroguanine as a result of direct bi-photonic ionization of guanine bases and indirect formation of guanine radical cations through hole transfer reactions from other base radical cations. The formation of 8-oxo-7,8-dihydroguanine and other purine and pyrimidine degradation products was rationalized in terms of the initial generation of related radical cations followed by either hydration or deprotonation reactions in agreement with mechanistic pathways inferred from detailed mechanistic studies. The guanine radical cation has been shown to be implicated in three other nucleophilic additions that give rise to DNA-protein and DNA-DNA cross-links in model systems. Evidence was recently provided for the occurrence of these three reactions in cellular DNA. Conclusion: There is growing evidence that one-electron oxidation reactions of nucleobases whose mechanisms have been characterized in model studies involving aqueous solutions take place in a similar way in cells. It may also be pointed out that the above cross-linked lesions are only produced from the guanine radical cation and may be considered as diagnostic products of the direct effect of ionizing radiation.

Original languageEnglish (US)
Pages (from-to)423-432
Number of pages10
JournalInternational Journal of Radiation Biology
Volume90
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Cations
Guanine
Electrons
DNA
Ionizing Radiation
Optics and Photonics
Oxidants
Hydroxyl Radical
pyrimidine
purine
Lasers
Proteins
8-hydroxyguanine

Keywords

  • DNA-protein cross-links
  • Intra and interstrand DNA cross-links
  • Ionizing radiation
  • One-electron oxidation
  • Oxidatively generated DNA damage

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

One-electron oxidation reactions of purine and pyrimidine bases in cellular DNA. / Cadet, Jean; Wagner, J. Richard; Shafirovich, Vladimir; Geacintov, Nicholas.

In: International Journal of Radiation Biology, Vol. 90, No. 6, 2014, p. 423-432.

Research output: Contribution to journalArticle

Cadet, Jean ; Wagner, J. Richard ; Shafirovich, Vladimir ; Geacintov, Nicholas. / One-electron oxidation reactions of purine and pyrimidine bases in cellular DNA. In: International Journal of Radiation Biology. 2014 ; Vol. 90, No. 6. pp. 423-432.
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