Clustered DNA Damage Induced by 2–20 eV Electrons and Transient Anions: General Mechanism and Correlation to Cell Death

Dong, Yanfang; Gao, Yujie; Liu, Wenhui; Gao, Ting; Zheng, Yi; Sanche, Léon

doi:10.1021/acs.jpclett.9b01063

Cited by 46 publications

(108 citation statements)

References 63 publications

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“…So far, DSBs have been the most investigated clustered lesions induced by LEE impact on DNA [67,86,94,95,96]. Figure 1 shows the energy dependence of the yields of DSBs from various film experiments in vacuum [67,86,95,96]. The yields in Figure 1A,C,D were obtained from the initial slopes of exposure–response curves, indicating the probability that a single electron will form a DSB.…”

Section: Clustered Dna Damages Induced By Leesmentioning

confidence: 99%

“…When created within the cell nucleus (i.e., close to the genome), LEEs are considered efficient and significant radiation-damage contributors. They can cause SSBs, DSBs, crosslinks, and base modifications in DNA [65,66,67], but it is mostly the unrepaired DNA clustered lesions that are responsible for mutagenic, genotoxic, and other potentially lethal effects in the cell. Therefore, finding the cause of such damages could help understand their destructive action in cancer cells and thus contribute to the development of new improved strategies for cancer treatment with radiotherapy and chemoradiation therapy [68,69].…”

Section: Introductionmentioning

confidence: 99%

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Clustered DNA Damages induced by 0.5 to 30 eV Electrons

Zheng

Sanche

2019

IJMS

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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.

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Section: Clustered Dna Damages Induced By Leesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clustered DNA Damages induced by 0.5 to 30 eV Electrons

Zheng

Sanche

2019

IJMS

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“…The type of damages induce by LEEs in DNA has been analyzed in detail by various techniques. It includes, base damage and cleavage, single and double strand breaks and other clustered lesions, consisting of strand breaks and base damages [11,[13][14][15][16]. Similar damages were observed and enhanced when GNPs were bound to DNA [17][18][19][20].…”

Section: Introductionmentioning

confidence: 73%

Concomitant Chemoradiation Therapy with Gold Nanoparticles and Platinum Drugs Co-Encapsulated in Liposomes

Charest

Tippayamontri

Shi

et al. 2020

IJMS

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A liposomal formulation of gold nanoparticles (GNPs) and carboplatin, named LipoGold, was produced with the staggered herringbone microfluidic method. The radiosensitizing potential of LipoGold and similar concentrations of non-liposomal GNPs, carboplatin and oxaliplatin was evaluated in vitro with the human colorectal cancer cell line HCT116 in a clonogenic assay. Progression of HCT116 tumor implanted subcutaneously in NU/NU mice was monitored after an irradiation of 10 Gy combined with either LipoGold, GNPs or carboplatin injected directly into the tumor by convection-enhanced delivery. Radiosensitization by GNPs alone or carboplatin alone was observed only at high concentrations of these compounds. Furthermore, low doses of carboplatin alone or a combination of carboplatin and GNPs did not engender radiosensitization. However, the same low doses of carboplatin and GNPs administered simultaneously by encapsulation in liposomal nanocarriers (LipoGold) led to radiosensitization and efficient control of cell proliferation. Our study shows that the radiosensitizing effect of a combination of carboplatin and GNPs is remarkably more efficient when both compounds are simultaneously delivered to the tumor cells using a liposomal carrier.

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“…Through their lyase and endonuclease activity, they convert base lesions into single strand breaks (SSB), inducing de novo DSBs and thus DNA fragmentation, which allows the detection of initial base lesions and SSBs through electrophoresis [16]. In plasmid DNA, the creation of de novo SSBs and subsequent DSBs through BER enzyme treatment is a result of the pre-existence of either complex base lesions or base lesions located in opposite strands already carrying a break within a short distance of a few nm (5-10 nm or 10-20 bp) [17]. The use of DNA repair enzymes as damage probes increases significantly the sensitivity of the detection by a factor of 2-5 [18].…”

Section: Introductionmentioning

confidence: 99%

In Situ Detection of Complex DNA Damage Using Microscopy: A Rough Road Ahead

Nikitaki

Pariset

Sudar

et al. 2020

Cancers

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Complexity of DNA damage is considered currently one if not the primary instigator of biological responses and determinant of short and long-term effects in organisms and their offspring. In this review, we focus on the detection of complex (clustered) DNA damage (CDD) induced for example by ionizing radiation (IR) and in some cases by high oxidative stress. We perform a short historical perspective in the field, emphasizing the microscopy-based techniques and methodologies for the detection of CDD at the cellular level. We extend this analysis on the pertaining methodology of surrogate protein markers of CDD (foci) colocalization and provide a unique synthesis of imaging parameters, software, and different types of microscopy used. Last but not least, we critically discuss the main advances and necessary future direction for the better detection of CDD, with important outcomes in biological and clinical setups.

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Clustered DNA Damage Induced by 2–20 eV Electrons and Transient Anions: General Mechanism and Correlation to Cell Death

Cited by 46 publications

References 63 publications

Clustered DNA Damages induced by 0.5 to 30 eV Electrons

Clustered DNA Damages induced by 0.5 to 30 eV Electrons

Concomitant Chemoradiation Therapy with Gold Nanoparticles and Platinum Drugs Co-Encapsulated in Liposomes

In Situ Detection of Complex DNA Damage Using Microscopy: A Rough Road Ahead

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