International Journal of Molecular Sciences

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11 pages, 1942 KiB

Open AccessArticle

Length and Energy Dependence of Low-Energy Electron-Induced Strand Breaks in Poly(A) DNA

by Kenny Ebel and Ilko Bald

Int. J. Mol. Sci. 2020, 21(1), 111; https://doi.org/10.3390/ijms21010111 - 23 Dec 2019

Cited by 9 | Viewed by 3275

Abstract

The DNA in living cells can be effectively damaged by high-energy radiation, which can lead to cell death. Through the ionization of water molecules, highly reactive secondary species such as low-energy electrons (LEEs) with the most probable energy around 10 eV are generated, [...] Read more.

The DNA in living cells can be effectively damaged by high-energy radiation, which can lead to cell death. Through the ionization of water molecules, highly reactive secondary species such as low-energy electrons (LEEs) with the most probable energy around 10 eV are generated, which are able to induce DNA strand breaks via dissociative electron attachment. Absolute DNA strand break cross sections of specific DNA sequences can be efficiently determined using DNA origami nanostructures as platforms exposing the target sequences towards LEEs. In this paper, we systematically study the effect of the oligonucleotide length on the strand break cross section at various irradiation energies. The present work focuses on poly-adenine sequences (d(A₄), d(A₈), d(A₁₂), d(A₁₆), and d(A₂₀)) irradiated with 5.0, 7.0, 8.4, and 10 eV electrons. Independent of the DNA length, the strand break cross section shows a maximum around 7.0 eV electron energy for all investigated oligonucleotides confirming that strand breakage occurs through the initial formation of negative ion resonances. When going from d(A₄) to d(A₁₆), the strand break cross section increases with oligonucleotide length, but only at 7.0 and 8.4 eV, i.e., close to the maximum of the negative ion resonance, the increase in the strand break cross section with the length is similar to the increase of an estimated geometrical cross section. For d(A₂₀), a markedly lower DNA strand break cross section is observed for all electron energies, which is tentatively ascribed to a conformational change of the dA₂₀ sequence. The results indicate that, although there is a general length dependence of strand break cross sections, individual nucleotides do not contribute independently of the absolute strand break cross section of the whole DNA strand. The absolute quantification of sequence specific strand breaks will help develop a more accurate molecular level understanding of radiation induced DNA damage, which can then be used for optimized risk estimates in cancer radiation therapy. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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18 pages, 14071 KiB

Open AccessArticle

Electron Transfer Induced Decomposition in Potassium–Nitroimidazoles Collisions: An Experimental and Theoretical Work

by Mónica Mendes, Gustavo García, Marie-Christine Bacchus-Montabonel and Paulo Limão-Vieira

Int. J. Mol. Sci. 2019, 20(24), 6170; https://doi.org/10.3390/ijms20246170 - 6 Dec 2019

Cited by 14 | Viewed by 2686

Abstract

Electron transfer induced decomposition mechanism of nitroimidazole and a selection of analogue molecules in collisions with neutral potassium (K) atoms from 10 to 1000 eV have been thoroughly investigated. In this laboratory collision regime, the formation of negative ions was time-of-flight mass analyzed [...] Read more.

Electron transfer induced decomposition mechanism of nitroimidazole and a selection of analogue molecules in collisions with neutral potassium (K) atoms from 10 to 1000 eV have been thoroughly investigated. In this laboratory collision regime, the formation of negative ions was time-of-flight mass analyzed and the fragmentation patterns and branching ratios have been obtained. The most abundant anions have been assigned to the parent molecule and the nitrogen oxide anion (NO₂^–) and the electron transfer mechanisms are comprehensively discussed. This work focuses on the analysis of all fragment anions produced and it is complementary of our recent work on selective hydrogen loss from the transient negative ions produced in these collisions. Ab initio theoretical calculations were performed for 4-nitroimidazole (4NI), 2-nitroimidazole (2NI), 1-methyl-4- (Me4NI) and 1-methyl-5-nitroimidazole (Me5NI), and imidazole (IMI) in the presence of a potassium atom and provided a strong basis for the assignment of the lowest unoccupied molecular orbitals accessed in the collision process. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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20 pages, 2366 KiB

Open AccessArticle

Charge Transfer, Complexes Formation and Furan Fragmentation Induced by Collisions with Low-Energy Helium Cations

by Tomasz J. Wasowicz, Marta Łabuda and Boguslaw Pranszke

Int. J. Mol. Sci. 2019, 20(23), 6022; https://doi.org/10.3390/ijms20236022 - 29 Nov 2019

Cited by 11 | Viewed by 3515

Abstract

The present work focuses on unraveling the collisional processes leading to the fragmentation of the gas-phase furan molecules under the He⁺ and He²⁺ cations impact in the energy range 5–2000 eV. The presence of different mechanisms was identified by the analysis [...] Read more.

The present work focuses on unraveling the collisional processes leading to the fragmentation of the gas-phase furan molecules under the He⁺ and He²⁺ cations impact in the energy range 5–2000 eV. The presence of different mechanisms was identified by the analysis of the optical fragmentation spectra measured using the collision-induced emission spectroscopy (CIES) in conjunction with the ab initio calculations. The measurements of the fragmentation spectra of furan were performed at the different kinetic energies of both cations. In consequence, several excited products were identified by their luminescence. Among them, the emission of helium atoms excited to the 1s4d ¹D₂, ³D_1,2,3 states was recorded. The structure of the furan molecule lacks an He atom. Therefore, observation of its emission lines is spectroscopic evidence of an impact reaction occurring via relocation of the electronic charge between interacting entities. Moreover, the recorded spectra revealed significant variations of relative band intensities of the products along with the change of the projectile charge and its velocity. In particular, at lower velocities of He⁺, the relative cross-sections of dissociation products have prominent resonance-like maxima. In order to elucidate the experimental results, the calculations have been performed by using a high level of quantum chemistry methods. The calculations showed that in both impact systems two collisional processes preceded fragmentation. The first one is an electron transfer from furan molecules to cations that leads to the neutralization and further excitation of the cations. The second mechanism starts from the formation of the He−C₄H₄O^+/2+ temporary clusters before decomposition, and it is responsible for the appearance of the narrow resonances in the relative cross-section curves. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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20 pages, 2901 KiB

Open AccessArticle

Radio-Enhancing Properties of Bimetallic Au:Pt Nanoparticles: Experimental and Theoretical Evidence

by Daniela Salado-Leza, Ali Traore, Erika Porcel, Diana Dragoe, Antonio Muñoz, Hynd Remita, Gustavo García and Sandrine Lacombe

Int. J. Mol. Sci. 2019, 20(22), 5648; https://doi.org/10.3390/ijms20225648 - 12 Nov 2019

Cited by 19 | Viewed by 3629

Abstract

The use of nanoparticles, in combination with ionizing radiation, is considered a promising method to improve the performance of radiation therapies. In this work, we engineered mono- and bimetallic core-shell gold–platinum nanoparticles (NPs) grafted with poly (ethylene glycol) (PEG). Their radio-enhancing properties were [...] Read more.

The use of nanoparticles, in combination with ionizing radiation, is considered a promising method to improve the performance of radiation therapies. In this work, we engineered mono- and bimetallic core-shell gold–platinum nanoparticles (NPs) grafted with poly (ethylene glycol) (PEG). Their radio-enhancing properties were investigated using plasmids as bio-nanomolecular probes and gamma radiation. We found that the presence of bimetallic Au:Pt-PEG NPs increased by 90% the induction of double-strand breaks, the signature of nanosize biodamage, and the most difficult cell lesion to repair. The radio-enhancement of Au:Pt-PEG NPs were found three times higher than that of Au-PEG NPs. This effect was scavenged by 80% in the presence of dimethyl sulfoxide, demonstrating the major role of hydroxyl radicals in the damage induction. Geant4-DNA Monte Carlo simulations were used to elucidate the physical processes involved in the radio-enhancement. We predicted enhancement factors of 40% and 45% for the induction of nanosize damage, respectively, for mono- and bimetallic nanoparticles, which is attributed to secondary electron impact processes. This work contributed to a better understanding of the interplay between energy deposition and the induction of nanosize biomolecular damage, being Monte Carlo simulations a simple method to guide the synthesis of new radio-enhancing agents. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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15 pages, 2469 KiB

Open AccessArticle

The Role of Electron Transfer in the Fragmentation of Phenyl and Cyclohexyl Boronic Acids

by Ana Isabel Lozano, Beatriz Pamplona, Tymon Kilich, Marta Łabuda, Mónica Mendes, João Pereira-da-Silva, Gustavo García, Pedro M. P. Gois, Filipe Ferreira da Silva and Paulo Limão-Vieira

Int. J. Mol. Sci. 2019, 20(22), 5578; https://doi.org/10.3390/ijms20225578 - 8 Nov 2019

Cited by 6 | Viewed by 3070

Abstract

In this study, novel measurements of negative ion formation in neutral potassium-neutral boronic acid collisions are reported in electron transfer experiments. The fragmentation pattern of phenylboronic acid is comprehensively investigated for a wide range of collision energies, i.e., from 10 to 1000 eV [...] Read more.

In this study, novel measurements of negative ion formation in neutral potassium-neutral boronic acid collisions are reported in electron transfer experiments. The fragmentation pattern of phenylboronic acid is comprehensively investigated for a wide range of collision energies, i.e., from 10 to 1000 eV in the laboratory frame, allowing some of the most relevant dissociation channels to be probed. These studies were performed in a crossed molecular beam set up using a potassium atom as an electron donor. The negative ions formed in the collision region were mass analysed with a reflectron time-of-flight mass spectrometer. In the unimolecular decomposition of the temporary negative ion, the two most relevant yields were assigned to BO⁻ and BO₂⁻. Moreover, the collision-induced reaction was shown to be selective, i.e., at energies below 100 eV, it mostly formed BO⁻, while at energies above 100 eV, it mostly formed BO₂⁻. In order to further our knowledge on the complex internal reaction mechanisms underlying the influence of the hybridization state of the boron atom, cyclohexylboronic acid was also investigated in the same collision energy range, where the main dissociation channel yielded BO₂⁻. The experimental results for phenyl boronic acid are supported by ab initio theoretical calculations of the lowest unoccupied molecular orbitals (LUMOs) accessed in the collision process. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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14 pages, 1484 KiB

Open AccessArticle

Cyclin D1 is Associated with Radiosensitivity of Triple-Negative Breast Cancer Cells to Proton Beam Irradiation

by Changhoon Choi, Sohee Park, Won Kyung Cho and Doo Ho Choi

Int. J. Mol. Sci. 2019, 20(19), 4943; https://doi.org/10.3390/ijms20194943 - 7 Oct 2019

Cited by 17 | Viewed by 4228

Abstract

Proton therapy offers a distinct physical advantage over conventional X-ray therapy, but its biological advantages remain understudied. In this study, we aimed to identify genetic factors that contribute to proton sensitivity in breast cancer (BC). Therefore, we screened relative biological effectiveness (RBE) of [...] Read more.

Proton therapy offers a distinct physical advantage over conventional X-ray therapy, but its biological advantages remain understudied. In this study, we aimed to identify genetic factors that contribute to proton sensitivity in breast cancer (BC). Therefore, we screened relative biological effectiveness (RBE) of 230 MeV protons, compared to 6 MV X-rays, in ten human BC cell lines, including five triple-negative breast cancer (TNBC) cell lines. Clonogenic survival assays revealed a wide range of proton RBE across the BC cell lines, with one out of ten BC cell lines having an RBE significantly different from the traditional generic RBE of 1.1. An abundance of cyclin D1 was associated with proton RBE. Downregulation of RB1 by siRNA or a CDK4/6 inhibitor increased proton sensitivity but not proton RBE. Instead, the depletion of cyclin D1 increased proton RBE in two TNBC cell lines, including MDA-MB-231 and Hs578T cells. Conversely, overexpression of cyclin D1 decreased the proton RBE in cyclin D1-deficient BT-549 cells. The depletion of cyclin D1 impaired proton-induced RAD51 foci formation in MDA-MB-231 cells. Taken together, this study provides important clues about the cyclin D1-CDK4-RB1 pathway as a potential target for proton beam therapy in TNBC. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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12 pages, 1645 KiB

Open AccessArticle

Ring Formation and Hydration Effects in Electron Attachment to Misonidazole

by Milan Ončák, Rebecca Meißner, Eugene Arthur-Baidoo, Stephan Denifl, Thomas F. M. Luxford, Andriy Pysanenko, Michal Fárník, Jiří Pinkas and Jaroslav Kočišek

Int. J. Mol. Sci. 2019, 20(18), 4383; https://doi.org/10.3390/ijms20184383 - 6 Sep 2019

Cited by 12 | Viewed by 3028

Abstract

We study the reactivity of misonidazole with low-energy electrons in a water environment combining experiment and theoretical modelling. The environment is modelled by sequential hydration of misonidazole clusters in vacuum. The well-defined experimental conditions enable computational modeling of the observed reactions. While the [...] Read more.

We study the reactivity of misonidazole with low-energy electrons in a water environment combining experiment and theoretical modelling. The environment is modelled by sequential hydration of misonidazole clusters in vacuum. The well-defined experimental conditions enable computational modeling of the observed reactions. While the NO

_{2}^{-}

dissociative electron attachment channel is suppressed, as also observed previously for other molecules, the OH

^{-}

channel remains open. Such behavior is enabled by the high hydration energy of OH

^{-}

and ring formation in the neutral radical co-fragment. These observations help to understand the mechanism of bio-reductive drug action. Electron-induced formation of covalent bonds is then important not only for biological processes but may find applications also in technology. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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14 pages, 2414 KiB

Open AccessArticle

Reactions in the Radiosensitizer Misonidazole Induced by Low-Energy (0–10 eV) Electrons

by Rebecca Meißner, Linda Feketeová, Eugen Illenberger and Stephan Denifl

Int. J. Mol. Sci. 2019, 20(14), 3496; https://doi.org/10.3390/ijms20143496 - 16 Jul 2019

Cited by 19 | Viewed by 3994

Abstract

Misonidazole (MISO) was considered as radiosensitizer for the treatment of hypoxic tumors. A prerequisite for entering a hypoxic cell is reduction of the drug, which may occur in the early physical-chemical stage of radiation damage. Here we study electron attachment to MISO and [...] Read more.

Misonidazole (MISO) was considered as radiosensitizer for the treatment of hypoxic tumors. A prerequisite for entering a hypoxic cell is reduction of the drug, which may occur in the early physical-chemical stage of radiation damage. Here we study electron attachment to MISO and find that it very effectively captures low energy electrons to form the non-decomposed molecular anion. This associative attachment (AA) process is exclusively operative within a very narrow resonance right at threshold (zero electron energy). In addition, a variety of negatively charged fragments are observed in the electron energy range 0–10 eV arising from dissociative electron attachment (DEA) processes. The observed DEA reactions include single bond cleavages (formation of NO₂⁻), multiple bond cleavages (excision of CN⁻) as well as complex reactions associated with rearrangement in the transitory anion and formation of new molecules (loss of a neutral H₂O unit). While any of these AA and DEA processes represent a reduction of the MISO molecule, the radicals formed in the course of the DEA reactions may play an important role in the action of MISO as radiosensitizer inside the hypoxic cell. The present results may thus reveal details of the molecular description of the action of MISO in hypoxic cells. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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14 pages, 1760 KiB

Open AccessArticle

5-Iodo-4-thio-2′-Deoxyuridine as a Sensitizer of X-ray Induced Cancer Cell Killing

by Samanta Makurat, Paulina Spisz, Witold Kozak, Janusz Rak and Magdalena Zdrowowicz

Int. J. Mol. Sci. 2019, 20(6), 1308; https://doi.org/10.3390/ijms20061308 - 15 Mar 2019

Cited by 13 | Viewed by 4251

Abstract

Nucleosides, especially pyrimidines modified in the C5-position, can act as radiosensitizers via a mechanism that involves their enzymatic triphosphorylation, incorporation into DNA, and a subsequent dissociative electron attachment (DEA) process. In this paper, we report 5-iodo-4-thio-2′-deoxyuridine (ISdU) as a compound that can effectively [...] Read more.

Nucleosides, especially pyrimidines modified in the C5-position, can act as radiosensitizers via a mechanism that involves their enzymatic triphosphorylation, incorporation into DNA, and a subsequent dissociative electron attachment (DEA) process. In this paper, we report 5-iodo-4-thio-2′-deoxyuridine (ISdU) as a compound that can effectively lead to ionizing radiation (IR)-induced cellular death, which is proven by a clonogenic assay. The test revealed that the survival of cells, pre-treated with 10 or 100 µM solution of ISdU and exposed to 0.5 Gy of IR, was reduced from 78.4% (for non-treated culture) to 67.7% and to 59.8%, respectively. For a somewhat higher dose of 1 Gy, the surviving fraction was reduced from 68.2% to 54.9% and to 40.8% for incubation with 10 or 100 µM ISdU, respectively. The cytometric analysis of histone H2A.X phosphorylation showed that the radiosensitizing effect of ISdU was associated, at least in part, with the formation of double-strand breaks. Moreover, the cytotoxic test against the MCF-7 breast cancer cell line and human dermal fibroblasts (HDFa line) confirmed low cytotoxic activity of ISdU. Based on the results of steady state radiolysis of ISdU with a dose of 140 Gy and quantum chemical calculations explaining the origin of the MS detected radioproducts, the molecular mechanism of sensitization by ISdU was proposed. In conclusion, we found ISdU to be a potential radiosensitizer that could improve anticancer radiotherapy. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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Review

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19 pages, 1088 KiB

Open AccessReview

Micronucleus Assay: The State of Art, and Future Directions

by Sylwester Sommer, Iwona Buraczewska and Marcin Kruszewski

Int. J. Mol. Sci. 2020, 21(4), 1534; https://doi.org/10.3390/ijms21041534 - 24 Feb 2020

Cited by 173 | Viewed by 17999

Abstract

During almost 40 years of use, the micronucleus assay (MN) has become one of the most popular methods to assess genotoxicity of different chemical and physical factors, including ionizing radiation-induced DNA damage. In this minireview, we focus on the position of MN among [...] Read more.

During almost 40 years of use, the micronucleus assay (MN) has become one of the most popular methods to assess genotoxicity of different chemical and physical factors, including ionizing radiation-induced DNA damage. In this minireview, we focus on the position of MN among the other genotoxicity tests, its usefulness in different applications and visibility by international organizations, such as International Atomic Energy Agency, Organization for Economic Co-operation and Development and International Organization for Standardization. In addition, the mechanism of micronuclei formation is discussed. Finally, foreseen directions of the MN development are pointed, such as automation, buccal cells MN and chromothripsis phenomenon. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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14 pages, 915 KiB

Open AccessReview

In Situ Analysis of DNA-Protein Complex Formation upon Radiation-Induced DNA Damage

by Giulio Ticli and Ennio Prosperi

Int. J. Mol. Sci. 2019, 20(22), 5736; https://doi.org/10.3390/ijms20225736 - 15 Nov 2019

Cited by 4 | Viewed by 3603

Abstract

The importance of determining at the cellular level the formation of DNA–protein complexes after radiation-induced lesions to DNA is outlined by the evidence that such interactions represent one of the first steps of the cellular response to DNA damage. These complexes are formed [...] Read more.

The importance of determining at the cellular level the formation of DNA–protein complexes after radiation-induced lesions to DNA is outlined by the evidence that such interactions represent one of the first steps of the cellular response to DNA damage. These complexes are formed through recruitment at the sites of the lesion, of proteins deputed to signal the presence of DNA damage, and of DNA repair factors necessary to remove it. Investigating the formation of such complexes has provided, and will probably continue to, relevant information about molecular mechanisms and spatiotemporal dynamics of the processes that constitute the first barrier of cell defense against genome instability and related diseases. In this review, we will summarize and discuss the use of in situ procedures to detect the formation of DNA-protein complexes after radiation-induced DNA damage. This type of analysis provides important information on the spatial localization and temporal resolution of the formation of such complexes, at the single-cell level, allowing the study of heterogeneous cell populations. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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15 pages, 2043 KiB

Open AccessReview

What Does the History of Research on the Repair of DNA Double-Strand Breaks Tell Us?—A Comprehensive Review of Human Radiosensitivity

by Elise Berthel, Mélanie L. Ferlazzo, Clément Devic, Michel Bourguignon and Nicolas Foray

Int. J. Mol. Sci. 2019, 20(21), 5339; https://doi.org/10.3390/ijms20215339 - 26 Oct 2019

Cited by 29 | Viewed by 4544

Abstract

Our understanding of the molecular and cellular response to ionizing radiation (IR) has progressed considerably. This is notably the case for the repair and signaling of DNA double-strand breaks (DSB) that, if unrepaired, can result in cell lethality, or if misrepaired, can cause [...] Read more.

Our understanding of the molecular and cellular response to ionizing radiation (IR) has progressed considerably. This is notably the case for the repair and signaling of DNA double-strand breaks (DSB) that, if unrepaired, can result in cell lethality, or if misrepaired, can cause cancer. However, through the different protocols, techniques, and cellular models used during the last four decades, the DSB repair kinetics and the relationship between cellular radiosensitivity and unrepaired DSB has varied drastically, moving from all-or-none phenomena to very complex mechanistic models. To date, personalized medicine has required a reliable evaluation of the IR-induced risks that have become a medical, scientific, and societal issue. However, the molecular bases of the individual response to IR are still unclear: there is a gap between the moderate radiosensitivity frequently observed in clinic but poorly investigated in the publications and the hyper-radiosensitivity of rare but well-characterized genetic diseases frequently cited in the mechanistic models. This paper makes a comprehensive review of semantic issues, correlations between cellular radiosensitivity and unrepaired DSB, shapes of DSB repair curves, and DSB repair biomarkers in order to propose a new vision of the individual response to IR that would be more coherent with clinical reality. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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22 pages, 4279 KiB

Open AccessReview

Ultrafast Processes Occurring in Radiolysis of Highly Concentrated Solutions of Nucleosides/Tides

by Jun MA, Sergey A. Denisov, Amitava Adhikary and Mehran Mostafavi

Int. J. Mol. Sci. 2019, 20(19), 4963; https://doi.org/10.3390/ijms20194963 - 8 Oct 2019

Cited by 26 | Viewed by 4867

Abstract

Among the radicals (hydroxyl radical (^•OH), hydrogen atom (H^•), and solvated electron (e_sol⁻)) that are generated via water radiolysis, ^•OH has been shown to be the main transient species responsible for radiation damage to DNA [...] Read more.

Among the radicals (hydroxyl radical (^•OH), hydrogen atom (H^•), and solvated electron (e_sol⁻)) that are generated via water radiolysis, ^•OH has been shown to be the main transient species responsible for radiation damage to DNA via the indirect effect. Reactions of these radicals with DNA-model systems (bases, nucleosides, nucleotides, polynucleotides of defined sequences, single stranded (ss) and double stranded (ds) highly polymeric DNA, nucleohistones) were extensively investigated. The timescale of the reactions of these radicals with DNA-models range from nanoseconds (ns) to microseconds (µs) at ambient temperature and are controlled by diffusion or activation. However, those studies carried out in dilute solutions that model radiation damage to DNA via indirect action do not turn out to be valid in dense biological medium, where solute and water molecules are in close contact (e.g., in cellular environment). In that case, the initial species formed from water radiolysis are two radicals that are ultrashort-lived and charged: the water cation radical (H₂O^•+) and prethermalized electron. These species are captured by target biomolecules (e.g., DNA, proteins, etc.) in competition with their inherent pathways of proton transfer and relaxation occurring in less than 1 picosecond. In addition, the direct-type effects of radiation, i.e., ionization of macromolecule plus excitations proximate to ionizations, become important. The holes (i.e., unpaired spin or cation radical sites) created by ionization undergo fast spin transfer across DNA subunits. The exploration of the above-mentioned ultrafast processes is crucial to elucidate our understanding of the mechanisms that are involved in causing DNA damage via direct-type effects of radiation. Only recently, investigations of these ultrafast processes have been attempted by studying concentrated solutions of nucleosides/tides under ambient conditions. Recent advancements of laser-driven picosecond electron accelerators have provided an opportunity to address some long-term puzzling questions in the context of direct-type and indirect effects of DNA damage. In this review, we have presented key findings that are important to elucidate mechanisms of complex processes including excess electron-mediated bond breakage and hole transfer, occurring at the single nucleoside/tide level. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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26 pages, 4841 KiB

Open AccessReview

Reaction of Electrons with DNA: Radiation Damage to Radiosensitization

by Anil Kumar, David Becker, Amitava Adhikary and Michael D. Sevilla

Int. J. Mol. Sci. 2019, 20(16), 3998; https://doi.org/10.3390/ijms20163998 - 16 Aug 2019

Cited by 66 | Viewed by 5718

Abstract

This review article provides a concise overview of electron involvement in DNA radiation damage. The review begins with the various states of radiation-produced electrons: Secondary electrons (SE), low energy electrons (LEE), electrons at near zero kinetic energy in water (quasi-free electrons, (e⁻ [...] Read more.

This review article provides a concise overview of electron involvement in DNA radiation damage. The review begins with the various states of radiation-produced electrons: Secondary electrons (SE), low energy electrons (LEE), electrons at near zero kinetic energy in water (quasi-free electrons, (e⁻_qf)) electrons in the process of solvation in water (presolvated electrons, e⁻_pre), and fully solvated electrons (e⁻_aq). A current summary of the structure of e⁻_aq, and its reactions with DNA-model systems is presented. Theoretical works on reduction potentials of DNA-bases were found to be in agreement with experiments. This review points out the proposed role of LEE-induced frank DNA-strand breaks in ion-beam irradiated DNA. The final section presents radiation-produced electron-mediated site-specific formation of oxidative neutral aminyl radicals from azidonucleosides and the evidence of radiosensitization provided by these aminyl radicals in azidonucleoside-incorporated breast cancer cells. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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16 pages, 2014 KiB

Open AccessReview

Clustered DNA Damages induced by 0.5 to 30 eV Electrons

by Yi Zheng and Léon Sanche

Int. J. Mol. Sci. 2019, 20(15), 3749; https://doi.org/10.3390/ijms20153749 - 31 Jul 2019

Cited by 24 | Viewed by 3927

Abstract

Low-energy electrons (LEEs) of energies ≤30 eV are generated in large quantities by ionizing radiation. These electrons can damage DNA; particularly, they can induce the more detrimental clustered lesions in cells. This type of lesions, which are responsible for a large portion of [...] Read more.

Low-energy electrons (LEEs) of energies ≤30 eV are generated in large quantities by ionizing radiation. These electrons can damage DNA; particularly, they can induce the more detrimental clustered lesions in cells. This type of lesions, which are responsible for a large portion of the genotoxic stress generated by ionizing radiation, is described in the Introduction. The reactions initiated by the collisions of 0.5–30 eV electrons with oligonucleotides, duplex DNA, and DNA bound to chemotherapeutic platinum drugs are explained and reviewed in the subsequent sections. The experimental methods of LEE irradiation and DNA damage analysis are described with an emphasis on the detection of cluster lesions, which are considerably enhanced in DNA–Pt–drug complexes. Based on the energy dependence of damage yields and cross-sections, a mechanism responsible for the clustered lesions can be attributed to the capture of a single electron by the electron affinity of an excited state of a base, leading to the formation of transient anions at 6 and 10 eV. The initial capture is followed by electronic excitation of the base and dissociative attachment—at other DNA sites—of the electron reemitted from the temporary base anion. The mechanism is expected to be universal in the cellular environment and plays an important role in the formation of clustered lesions. Full article

(This article belongs to the Special Issue Radiation-Induced Damage to DNA)

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