Low‐Energy Electron Interaction with DNA: Bond Dissociation and Formation of Transient Anions, Radicals, and Radical Anions

Sanche, Léon

doi:10.1002/9780470526279.ch9

Cited by 59 publications

(173 citation statements)

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“…The results presented in Ref. [1] motivated a large amount of both experimental [11,30,31,32,33] and theoretical [34,35,36] work that aimed at elucidating the role played by LEE in DNA damage. In recent years, this research has moved on from idealized systems, e.g.…”

Section: Radiation Damage Of Dnamentioning

confidence: 99%

Interactions between low energy electrons and DNA: a perspective from first-principles simulations

Kohanoff¹,

McAllister²,

Tribello³

et al. 2017

J. Phys.: Condens. Matter

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Abstract. DNA damage caused by irradiation has been studied for many decades. Such studies allow us to better assess the dangers posed by radiation, and to increase the efficiency of the radiotherapies that are used to combat cancer. A full description of the irradiation process involves multiple size and time scales. It starts from the interaction of radiation -either photons or swift ions -with the biological medium. Such interactions cause electronic excitation and ionisation. The two main products of ionising radiation are thus electrons and radicals. Both of these species can cause damage to biological molecules, in particular DNA. In the long run, this molecular level damage can prevent cells from replicating and can hence lead to cell death. For a long time it was assumed that the main actors in the damage process were the radicals. However, experiments in a seminal paper by the group of Leon Sanche in 2000 showed that low-energy electrons (LEE), such as those generated when ionising biological targets, can also cause bond breaks in biomolecules, in particular strand breaks in plasmid DNA [1]. These results prompted a significant amount of experimental and theoretical work aimed at elucidating the role played by LEE in DNA damage.In this Topical Review we provide a general overview of the problem. We discuss experimental findings and theoretical results hand in hand with the aim of describing the physics and chemistry that occurs during the process of radiation damage, from the initial stages of electronic excitation, through the inelastic propagation of electrons in the medium, the interaction of electrons with DNA, and the chemical end-point effects on DNA. A very important aspect of this discussion is the consideration of a realistic, physiological environment. The role played by the aqueous solution and the amino acids from the histones in chromatin must be considered. Moreover, thermal fluctuations must be incorporated when studying these phenomena. Hence, a special place in this Topical Review is occupied by our recent first-principles molecular dynamics simulations that address the issue of how the environment favours or prevents LEEs from causing damage to DNA. We finish by summarising the conclusions achieved so far, and by suggesting a number of possible directions for further study.

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Section: Radiation Damage Of Dnamentioning

confidence: 99%

Interactions between low energy electrons and DNA: a perspective from first-principles simulations

Kohanoff¹,

McAllister²,

Tribello³

et al. 2017

J. Phys.: Condens. Matter

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“…2,3 LEEs can also transfer from one DNA subunit to another, particularly from a base to the phosphate group, where they can induce cleavage of the C-O bond (i.e., break a DNA strand). 2 Since LEEs contain a large fraction of the energy deposited by high-energy particles, 5,6 these results are relevant to a precise understanding of the mechanisms of the direct effect of DNA damage induced by high-energy radiation and its application to radiotherapy. In fact, it has recently been shown that the modification of these fundamental mechanisms by chemotherapeutic agents considerably increases DNA damage.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] It is now established that, for energies below 15 eV, LEEs localize on the DNA subunits to form transient negative ions (TNIs). [2][3][4] These latter can damage DNA by dissociating into a stable anion and one or more radical fragments (i.e., by dissociative electron attachment (DEA)) or by decaying into dissociative electronically excited states. 2,3 LEEs can also transfer from one DNA subunit to another, particularly from a base to the phosphate group, where they can induce cleavage of the C-O bond (i.e., break a DNA strand).…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] These latter can damage DNA by dissociating into a stable anion and one or more radical fragments (i.e., by dissociative electron attachment (DEA)) or by decaying into dissociative electronically excited states. 2,3 LEEs can also transfer from one DNA subunit to another, particularly from a base to the phosphate group, where they can induce cleavage of the C-O bond (i.e., break a DNA strand). 2 Since LEEs contain a large fraction of the energy deposited by high-energy particles, 5,6 these results are relevant to a precise understanding of the mechanisms of the direct effect of DNA damage induced by high-energy radiation and its application to radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…2 Although dry film experiments in vacuum were essential to unveil basic mechanisms of damage, they clearly do not correspond to cellular conditions. Thus, a series of experiments were recently undertaken to add to vacuum DNA other components found in the cell nucleus, so as to systematically investigate modifications of the mechanisms of action of LEEs by molecular constituents of the nucleus.…”

Section: Introductionmentioning

confidence: 99%

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Low energy electron stimulated desorption from DNA films dosed with oxygen

Mirsaleh-Kohan

Bass

Cloutier

et al. 2012

The Journal of Chemical Physics

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Desorption of anions stimulated by 1-18 eV electron impact on self-assembled monolayer (SAM) films of single DNA strands is measured as a function of film temperature (50-250 K). The SAMs, composed of 10 nucleotides, are dosed with O 2 . The OH − desorption yields increase markedly with exposure to O 2 at 50 K and are further enhanced upon heating. In contrast, the desorption yields of O − , attributable to dissociative electron attachment to trapped O 2 molecules decrease with heating. Irradiation of the DNA films prior to the deposition of O 2 shows that this surprising increase in OH − desorption, at elevated temperatures, arises from the reaction of O 2 with damaged DNA sites. These results thus appear to be a manifestation of the so-called "oxygen fixation" effect, well known in radiobiology.

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Contribution of Base Damages to the Molecular Radiosensitization Mechanism of Platinum Chemotherapeutic Drugs

et al. 2019

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The measurement of clustered damages in Pt‐chemotherapeutic‐drugs‐DNA complexes induced by low‐energy (0‐30 eV) electrons (LEEs) may provide further understanding of the synergy mechanism in cancer treatment with concomitant chemoradiation therapy (CRT). Five‐monolayer films of Pt‐DNA complexes, containing cisplatin, carboplatin and oxaliplatin with ratio 5:1 were irradiated with mono‐energetic electrons of 10 eV, the most prominent energy for bond dissociation by LEE impact. Damages to plasmid DNA including crosslinks, SSBs, DSBs and the loss of the supercoiled configuration were analyzed by the electrophoresis. Base damages (BDs) occurring within two turns of DNA helix were detected by the treatment of E. coli base excision repair endonuclease (Nth and Fpg). The total DNA damages to Pt‐DNA complexes was found to be 350 ± 42, 296 ± 45 and 434 ± 46 ×10−15 electron−1molecule−1, respectively, while the percentages of BDs in this total were 56%, 54% and 60%, respectively. Compared to unmodified DNA, binding of Pt‐drugs to DNA increased BDs by factors of 1.9, 1.6 and 2.6, respectively, which partly resulted in significant enhancements of potentially lethal lesions (i. e., crosslinks, double strand breaks (DSBs) and non‐DSB cluster damages). These results reveal the significant role that LEEs play in the formation of clustered DNA damages related to BDs, which are expected to contribute to the higher efficacy of cancer treatment by CRT with the Pt‐drugs investigated.

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Low‐Energy Electron Interaction with DNA: Bond Dissociation and Formation of Transient Anions, Radicals, and Radical Anions

Cited by 59 publications

References 145 publications

Interactions between low energy electrons and DNA: a perspective from first-principles simulations

Interactions between low energy electrons and DNA: a perspective from first-principles simulations

Low energy electron stimulated desorption from DNA films dosed with oxygen

Contribution of Base Damages to the Molecular Radiosensitization Mechanism of Platinum Chemotherapeutic Drugs

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