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Journal ArticleDOI

Resonant Formation of DNA Strand Breaks by Low-Energy (3 to 20 eV) Electrons

03 Mar 2000-Science (American Association for the Advancement of Science)-Vol. 287, Iss: 5458, pp 1658-1660
TL;DR: It is shown that reactions of such electrons, even at energies well below ionization thresholds, induce substantial yields of single- and double-strand breaks in DNA, which are caused by rapid decays of transient molecular resonances localized on the DNA's basic components.
Abstract: Most of the energy deposited in cells by ionizing radiation is channeled into the production of abundant free secondary electrons with ballistic energies between 1 and 20 electron volts. Here it is shown that reactions of such electrons, even at energies well below ionization thresholds, induce substantial yields of single- and double-strand breaks in DNA, which are caused by rapid decays of transient molecular resonances localized on the DNA's basic components. This finding presents a fundamental challenge to the traditional notion that genotoxic damage by secondary electrons can only occur at energies above the onset of ionization, or upon solvation when they become a slowly reacting chemical species.
Citations
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Journal ArticleDOI
TL;DR: It was found that the structure and morphology also affect the energy transport among tissue constituents and therefore the ablation efficiency of biological tissues is increased.
Abstract: Author(s): Vogel, Alfred; Venugopalan, Vasan | Abstract: The mechanisms of pulsed laser ablation of biological tissues were studied. The transiently empty space created between the fiber tip and the tissue surface improved the optical transmission to the target and thus increased the ablation efficiency. It was found that the structure and morphology also affect the energy transport among tissue constituents.

1,861 citations

Journal ArticleDOI
TL;DR: In this article, the working mechanisms of femtosecond laser nanoprocessing in biomaterials with oscillator pulses of 80-MHz repetition rate and with amplified pulses of 1-kHz repetition rate were investigated.
Abstract: We review recent advances in laser cell surgery, and investigate the working mechanisms of femtosecond laser nanoprocessing in biomaterials with oscillator pulses of 80-MHz repetition rate and with amplified pulses of 1-kHz repetition rate. Plasma formation in water, the evolution of the temperature distribution, thermoelastic stress generation, and stress-induced bubble formation are numerically simulated for NA=1.3, and the outcome is compared to experimental results. Mechanisms and the spatial resolution of femtosecond laser surgery are then compared to the features of continuous-wave (cw) microbeams. We find that free electrons are produced in a fairly large irradiance range below the optical breakdown threshold, with a deterministic relationship between free-electron density and irradiance. This provides a large ‘tuning range’ for the creation of spatially extremely confined chemical, thermal, and mechanical effects via free-electron generation. Dissection at 80-MHz repetition rate is performed in the low-density plasma regime at pulse energies well below the optical breakdown threshold and only slightly higher than used for nonlinear imaging. It is mediated by free-electron-induced chemical decomposition (bond breaking) in conjunction with multiphoton-induced chemistry, and hardly related to heating or thermoelastic stresses. When the energy is raised, accumulative heating occurs and long-lasting bubbles are produced by tissue dissociation into volatile fragments, which is usually unwanted. By contrast, dissection at 1-kHz repetition rate is performed using more than 10-fold larger pulse energies and relies on thermoelastically induced formation of minute transient cavities with lifetimes <100 ns. Both modes of femtosecond laser nanoprocessing can achieve a 2–3 fold better precision than cell surgery using cw irradiation, and enable manipulation at arbitrary locations.

1,226 citations

Journal ArticleDOI
TL;DR: The field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials is introduced, and the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed.
Abstract: Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed.

884 citations


Cites methods from "Resonant Formation of DNA Strand Br..."

  • ...Boudaiffa et al [58] used the DNA plasmid model to demonstrate that very LEEs (,20 eV), which do not have enough energy to cause direct ionisation of DNA or other...

    [...]

  • ...S Jain, D G Hirst and J M O’Sullivan 104 The British Journal of Radiology, February 2012 Boudaiffa et al [58] used the DNA plasmid model to demonstrate that very LEEs (,20 eV), which do not have enough energy to cause direct ionisation of DNA or other molecules (such as water), were capable of causing DNA damage....

    [...]

Journal ArticleDOI
TL;DR: Chemical mechanisms for IR-induced modifications of biomolecules along with methods for their detection are described and the synergy of combined "omics" technologies such as genomics and epigenomics, proteomics, and metabolomics is highlighted.
Abstract: Significance: The detrimental effects of ionizing radiation (IR) involve a highly orchestrated series of events that are amplified by endogenous signaling and culminating in oxidative damage to DNA, lipids, proteins, and many metabolites. Despite the global impact of IR, the molecular mechanisms underlying tissue damage reveal that many biomolecules are chemoselectively modified by IR. Recent Advances: The development of high-throughput “omics” technologies for mapping DNA and protein modifications have revolutionized the study of IR effects on biological systems. Studies in cells, tissues, and biological fluids are used to identify molecular features or biomarkers of IR exposure and response and the molecular mechanisms that regulate their expression or synthesis. Critical Issues: In this review, chemical mechanisms are described for IR-induced modifications of biomolecules along with methods for their detection. Included with the detection methods are crucial experimental considerations and cav...

487 citations

References
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Journal ArticleDOI
TL;DR: In this article, a common range of attachment energies into the lowest orbitals is observed in all the bases, and evidence for nuclear motion during the lifetimes of the anions is found in all compounds except adenine.
Abstract: Injection of electrons into the empty π* molecular orbitals of uracil and the DNA bases creates short-lived anion states whose energies have been determined by electron scattering. A common range of attachment energies into the lowest orbitals is observed in all the bases. Evidence for nuclear motion during the lifetimes of the anions is found in all the compounds except adenine. These properties of the bases as bridge sites along the π-stack of DNA, namely, the effective degeneracy of the anion energies and the strong excitation of vibration, are key parameters for theories of electron-transfer rate, some of which lead to inverse rather than exponentially decreasing bridge-length dependences.

359 citations

Journal ArticleDOI
TL;DR: Frongillo et al. as mentioned in this paper used Monte Carlo simulation techniques to model the sequence of events that are generated by the interaction of ionising radiations with pure liquid water, including the energy depositions that occur through the ionisation and the excitation of water molecules, and the relaxation pathways and the ultrafast reactions of the subexcitation electrons, of the transient water anions and cations, and of the excited water molecules.

352 citations

Journal ArticleDOI
TL;DR: The authors' measurements suggest that this resonant mechanism may relate to critical damage of irradiated cellular DNA by subionization electrons prior to thermalization.
Abstract: We have measured the electron energy dependence for production of a great variety of anion fragments, induced by resonant attachment of subionization electrons to thymine (T) and cytosine (C) within femto-second time scales. At the lowest electron energies we also observe stable molecular anions of these bases, viz., T− and C−. Our measurements suggest that this resonant mechanism may relate to critical damage of irradiated cellular DNA by subionization electrons prior to thermalization.

237 citations

Journal ArticleDOI
TL;DR: In this article, a series of negative ion photoelectron spectroscopic experiments on gas-phase, solvated uracil cluster anions were conducted to investigate the transformation from one form into another due to environmental (solvation) effects.
Abstract: Nucleic acid base anions play an important role in radiation-induced mutagenesis. Recently, it has been shown that isolated (gas-phase) nucleobases form an exotic form of negative ions, namely, dipole bound anions. These are species in which the excess electrons are bound by the dipole fields of the neutral molecules. In the condensed phase, on the other hand, nucleobase anions are known to be conventional (covalent) anions, implying the transformation from one form into the other due to environmental (solvation) effects. Here, in a series of negative ion photoelectron spectroscopic experiments on gas-phase, solvated uracil cluster anions, we report the observation of this transformation.

235 citations

Journal ArticleDOI
TL;DR: The results of this study suggest that the release of bases originating from irradiation of the hydration water is obtained predominantly by charge transfer from the direct ionization of the first 12-15 water molecules of the primary hydration layer and by the attack of hydroxyl radicals generated in the outer, more loosely bound water molecules.
Abstract: The release of unaltered bases from irradiated DNA, hydrated between 2.5 and 32.7 mol of water per mole of nucleotide (Γ), was investigated using HPLC. The objective of this study was to elucidate the yield of the four DNA bases as a function of dose, extent of hydration, and the presence or absence of oxygen. The increase in the yield of radiation-induced free bases was linear with dose up to 90 kGy, except for the DNA with Γ = 2.5, for which the increase was linear only to 10 kGy. The yield of free bases as a function of Γ was not constant in either the absence or the presence of oxygen over the range of hydration examined. For DNA with Γ between 2.5 and 15, the yield of free bases was nearly constant under nitrogen, but decreased under oxygen. However, for DNA with Γ > 15, the yield increased rapidly under both nitrogen and oxygen. The yield of free bases was described by a model that depended on two factors: 1) a change in the DNA conformation from a mixture of the A and C conformers in vacuum-dried D...

196 citations