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Journal Articles

Radon inhalation decreases DNA damage induced by oxidative stress in mouse organs via the activation of antioxidative functions

Kataoka, Takahiro*; Shuto, Hina*; Naoe, Shota*; Yano, Junki*; Kanzaki, Norie; Sakoda, Akihiro; Tanaka, Hiroshi; Hanamoto, Katsumi*; Mitsunobu, Fumihiro*; Terato, Hiroaki*; et al.

Journal of Radiation Research (Internet), 62(5), p.861 - 867, 2021/09

 Times Cited Count:5 Percentile:71.17(Biology)

Journal Articles

Evaluation of DNA damage induced by Auger electrons from $$^{137}$$Cs

Watanabe, Ritsuko; Hattori, Yuya; Kai, Takeshi

International Journal of Radiation Biology, 92(11), p.660 - 664, 2016/11

 Times Cited Count:2 Percentile:21.33(Biology)

To understand the effect of internal exposure of $$^{137}$$Cs, we focus on estimation of microscopic energy deposition pattern and DNA damage induced by directly emitted electrons (beta-rays, internal conversion electrons, Auger electrons) from $$^{137}$$Cs. Monte Carlo track simulation method was used to calculate the microscopic energy deposition pattern. To simulate the energy deposition by directly emitted electrons, we considered the multiple ejections of electrons after internal conversion. Induction process of DNA strand breaks and base lesions was modeled and simulated using Monte Carlo methods for cell mimetic condition. The yield and spatial distribution of simple and complex DNA damage were calculated for the cases of $$gamma$$-rays and electrons from $$^{137}$$Cs. The simulation showed that significant difference of DNA damage spectrum was not caused by the difference between secondary electron spectrum by $$gamma$$-rays and directly ejected electron spectrum. The result support that the existing evaluation that internal exposure and external exposure are almost equivalent.

Journal Articles

Deceleration processes of secondary electrons produced by a high-energy Auger electron in a biological context

Kai, Takeshi; Yokoya, Akinari; Ukai, Masatoshi; Fujii, Kentaro; Watanabe, Ritsuko

International Journal of Radiation Biology, 92(11), p.654 - 659, 2016/11

 Times Cited Count:8 Percentile:63.78(Biology)

Journal Articles

Editorial: Maintenance of genome integrity; DNA damage sensing, signaling, repair, and replication in plants

Balestrazzi, A.*; Achary V Mohan Murali*; Macovei, A.*; Yoshiyama, Kaoru*; Sakamoto, Ayako

Frontiers in Plant Science (Internet), 7, p.64_1 - 64_2, 2016/02

 Times Cited Count:3 Percentile:58.05(Plant Sciences)

no abstracts in English

Journal Articles

Nitrogen K-edge X-ray absorption near edge structure of pyrimidine-containing nucleotides in aqueous solution

Shimada, Hiroyuki*; Minami, Hirotake*; Okuizumi, Naoto*; Sakuma, Ichiro*; Ukai, Masatoshi*; Fujii, Kentaro; Yokoya, Akinari; Fukuda, Yoshihiro*; Saito, Yuji

Journal of Chemical Physics, 142(17), p.175102_1 - 175102_9, 2015/05


 Times Cited Count:10 Percentile:40.9(Chemistry, Physical)

Journal Articles

Nitrogen K-edge X-ray absorption near edge structure (XANES) spectra of purine-containing nucleotides in aqueous solution

Shimada, Hiroyuki*; Fukao, Taishi*; Minami, Hirotake*; Ukai, Masatoshi*; Fujii, Kentaro; Yokoya, Akinari; Fukuda, Yoshihiro*; Saito, Yuji

Journal of Chemical Physics, 141(5), p.055102_1 - 055102_8, 2014/08

 Times Cited Count:15 Percentile:53.72(Chemistry, Physical)

Journal Articles

Yields of strand breaks and base lesions induced by soft X-rays in plasmid DNA

Yokoya, Akinari; Fujii, Kentaro; Ushigome, Takeshi; Shikazono, Naoya; Urushibara, Ayumi; Watanabe, Ritsuko

Radiation Protection Dosimetry, 122(1-4), p.86 - 88, 2006/12

 Times Cited Count:11 Percentile:61.07(Environmental Sciences)

We have studied yields of DNA damages induced by soft X-rays obtained from a conventional soft X-ray machine in a LET region between $$gamma$$-rays and ultrasoft X-rays. Practically soft X-rays with a broad energy spectrum emitted from a target of heavy metal, such as tungsten, have been widely used not only for radiobiological experiments but also for medical application such as mammography. Radiation weighting factors for these soft X-rays have been assigned to be 1 by ICRP. However, the fraction of a large number of low energy photons in the spectrum (below several tens keV) provided by bremsstrahlung is expected to be more effective for DNA damage induction than $$gamma$$-rays since low energy photo- and Auger electrons predominantly ejected in consequence of a photoelectric effect can produce dense clusters of ionization/excitation on DNA molecules. We have examined the yield of DNA strand breaks induced by white soft X-rays (150 kVp, tungsten target). Yields of base lesions revealed by base excision repair enzymes will be also presented.

Journal Articles

Clustered DNA damage induced by ionizing radiaton

Yokoya, Akinari; Shikazono, Naoya; Urushibara, Ayumi; Fujii, Kentaro; Akamatsu, Ken; Watanabe, Ritsuko

Hoshasen Seibutsu Kenkyu, 40(2), p.168 - 184, 2005/06

Ionizing radiation causes modifications in a DNA molecule depending on the characteristic tack-structure in which two or more isolated lesions arise in a few nm scale (1 or 2 helical turn of DNA), known as "clustered DNA damage". These clustered DNA damages could be distinct from those by reactive oxygen species (ROS) endogenously induced on their severity of induction of biological effects such as mutation. However, the studies on the nature and repair mechanism of clustered DNA damage have still been behind because of the technical difficulties on determination of the chemical structure and yield. This article reviews some experimental evidences of the clustered DNA damages in this research field, as well as our recent progress on the studies on the clustered DNA damages using both molecular biological techniques and synchrotron spectroscopic method.

Journal Articles

Molecular dynamics simulation of clustered DNA damage sites containing 8-oxoguanine and abasic site

Fujimoto, Hirofumi*; Pinak, M.; Nemoto, Toshiyuki*; O'Neill, P.*; Kume, Etsuo; Saito, Kimiaki; Maekawa, Hideaki*

Journal of Computational Chemistry, 26(8), p.788 - 798, 2005/06

 Times Cited Count:23 Percentile:57.55(Chemistry, Multidisciplinary)

Clustered DNA damage sites induced by ionizing radiation have been suggested to have serious consequences to organisms. In this study, approaches based on molecular dynamics (MD) simulation have been applied to examine conformational changes and energetic properties of DNA molecules containing clustered damage sites consisting of 2 lesioned sites, 8-oxoG and AP site. After 1 nanosecond of MD simulation, one of the 6 DNA molecules containing a clustered damage site develop specific characteristic features: sharp bending at the lesioned site and weakening or complete loss of electrostatic interaction energy between 8-oxoG and bases locating on the complementary strand. From these results it is suggested that these changes would make it difficult for the repair enzyme to bind to the lesions within the clustered damage site and thereby result in a reduction of its repair capacity.

JAEA Reports

Molecular dynamics simulation studies of radiation damaged DNA molecules and repair enzymes

Pinak, M.

JAERI 1346, 25 Pages, 2004/12


Molecular dynamics (MD) studies on several radiation damages to DNA - thymine dimer, thymine glycol8-oxoguanine and their recognition by repair enzymes are introduced in order to describe on the stepwise description of molecular process observed at radiation lesion sites. In all cases the significant structural changes in the DNA double helical structure were observed: (a) the breaking of hydrogen bonds network between complementary bases and resulting opening of the double helix (8-oxoguanine); (b) the sharp bending of the DNA helix centered at the lesion site (thymine dimer, thymine glycol); and (c) the flipping-out base on the strand complementary to the lesion (8-oxoguanine). The specific values of electrostatic interaction energy were found at the lesion sites (thymine dimmer: -10kcal/mol, thymine glycol: -26kcal/mol, 8-oxoguanine: -48kcal/mol).

Journal Articles

EPR studies of 5-bromouracil crystal after irradiation with X-rays in the bromine K-edge region

Yokoya, Akinari; Takakura, Kaoru*; Watanabe, Ritsuko; Akamatsu, Ken*; Ito, Takashi*

Radiation Research, 162(4), p.469 - 473, 2004/10

Radicals induced in a single crystal of 5-bromouracil (BrUra) by synchrotron soft X-rays in the Br K-edge region (13.461-13482 keV) were investigated using the X-band EPR method. The crystal was irradiated at three peak energies in the absorption spectrum at room temperature or at 80K. A hydrogen abstraction radical derived from N1 atom of the pyrimidine ring was commonly observed for all of the energies used, though with some variation in quantity. Similar characteristics were also observed in the EPR signal for the off-K-edge low energy (13.42 keV) and when $$^{60}$$Co $$gamma$$-ray irradiation was employed as the reference. When irradiated at 80K, a much larger exposure (roughly 10 times) of soft X-rays was needed to obtain the same signal intensity as that observed at room temperature. EPR signals were not detectable with g-irradiation at liquid nitrogen temperature.

Journal Articles

EPR studies of 5-bromouracil crystal after irradiation with X rays in the bromine K-edge region

Yokoya, Akinari; Takakura, Kaoru*; Watanabe, Ritsuko; Akamatsu, Ken*; Ito, Takashi*

Radiation Research, 162(4), p.469 - 473, 2004/10

 Times Cited Count:3 Percentile:10.27(Biology)

X-ray absorption spectra from single crystals of 5-Bromouracil were measured with the transmission mode in the energy range from 13.41 to 13.50 keV using the linearly polarized synchrotron radiation (SR). A characteristic resonance structure, consisting of four peaks, was recognized in the spectra in the Br K-edge region. The intensities of these peaks were strongly dependent on the crystal rotation about the normal of the crystal b-c plane, which was set perpendicular to the X-ray beam direction. (SR X-rays are polarized in the horizontal plane.) Molecular orbital calculations indicate that these resonance peaks are associated with the transitions from the 1s electron of Br to the Br-C molecular antibonding orbitals and to a shape resonance. The observed anisotropy of each photoabsorption peak might originate from the angular dependences of these molecular orbitals.

Journal Articles

Production mechanism of DNA bases radical induced by inner-shell excitation

Yokoya, Akinari

Hoshako, 17(3), p.111 - 117, 2004/05

To reveal the mechanism of oxidative base damages, such as 8-oxo-G, in DNA molecule by ionizing radiation, DNA base radicals were examined around oxygen and nitrogen K-edge region using an EPR spectrometer installed in a synchrotron soft X-ray beamline (BL23SU) in SPring-8. In situ measurements of EPR spectrum of guanine base revealed that short-lived transient radical species are specifically induced by photoexcitation of a 1s electron to $$sigma$$* antibonding orbital at carbonyl oxygen atom. They promptly disappear by "beam-off". On the other hand, a long-lived radical whose EPR spectrum is consistent with previous reports for guanine cation radical was accumulated during the irradiation. The yield of the stable radical decreased by These results indicate that chemically stable DNA base lesions, such as 8-oxo-G, would result from transient species that are inferred to be one electron oxidized radicals after decay of Auger final state.

Journal Articles

Impact of radiation damage on DNA determined by computational simulation

Pinak, M.

Hoken Butsuri, 39(1), p.35 - 41, 2004/03

Review of molecular dynamics (MD) studies of several radiation-originated lesions on DNA molecules is presented. Main focus is to describe structural and energy changes in DNA molecule with the respect to proper recognition of the lesion by respective repair enzyme. In most cases the observed changes are related to overall collapsing of the double helical structure around the lesion and are considered to facilitate docking of the repair enzyme into the DNA and formation of DNA-enzyme complex. Stable DNA-enzyme complex is necessary condition for the onset of entire enzymatic repair process. In addition to the structural changes, specific values of electrostatic interaction energy are detected at several lesion sites. The specific electrostatic energy is considered as a factor that enables repair enzyme to discriminate lesion from native, non-damaged site.

Journal Articles

Large scale MD simulation of 8-oxoguanine and AP site multiple lesioned DNA molecule combined with biomolecular visualization software

Fujimoto, Hirofumi; Pinak, M.; Nemoto, Toshiyuki*; Sakamoto, Kiyotaka*; Yamada, Kazuyuki*; Hoshi, Yoshiyuki*; Kume, Etsuo

Journal of Molecular Structure; THEOCHEM, 681(1-3), p.1 - 8, 2004/01

We developed the novel system, Fujitsu Bio Molecular Visualization System (F-BMVS), that enables to produce real pictures and an animation by arranging them along a time series of a large scale simulation of biomolecules associated with a molecular dynamics (MD) simulation program. This animation system is used to study the results of molecular dynamics code, AMBER, in order to find structural differences on the lesioned DNA comparing with non-damaged DNA. These structural differences would be a factor that guides a repair enzyme to discriminate a lesion from non-damaged DNA region.

JAEA Reports

Selected materials of the international workshop on radiation risk and its origin at molecular and cellular level; February 6-7, 2003

Pinak, M.

JAERI-Conf 2003-011, 113 Pages, 2003/09


The workshop "International Workshop on Radiation Risk and its Origin at Molecular and Cellular Level" was held at The Tokai Research Establishment, Japan Atomic Energy Research Institute, on the 6th and 7th of February 2003. The Laboratory of Radiation Risk Analysis of JAERI organized it. This international workshop attracted scientists from several different scientific areas, including radiation physics, radiation biology, molecular biology, crystallography of biomolecules, modeling and bio-informatics. Several foreign and domestic keynote speakers addresses the very fundamental areas of radiation risk and tried to establish a link between the fundamental studies at the molecular and cellular level and radiation damages at the organism. The symposium consisted of 13 oral lectures, 10 poster presentations and panel discussion. The 108 participants attended the workshop. This publication comprises of proceedings of oral and poster presentations where available. For the rest of contributions the abstracts or/and selections of presentation materials are shown instead.

JAEA Reports

Achievement in research on ion beam application under the scientific cooperation program with the Gesellschaft f$"u$r Schwerionenforschung mbH

Yoshida, Masaru; Maekawa, Yasunari

JAERI-Review 2003-002, 30 Pages, 2003/03


The Japan Atomic Energy Research Institute (JAERI) and the Gesellschaft fur Schwerionenforschung mbH (GSI) signed a memorandum of "Research and Development in the Field of Ion Beam Application" in January, 1991 and started the cooperative research program. The cooperation has been implemented by means of joint research between JAERI and GSI, exchange of scientific and technical experts, and providing mutual exchange of research materials as well as technical information. This report summarizes the cooperative research activities under the cooperative research program in the last 12 years.

Journal Articles

Effects of hydration on the induction of strand breaks, base lesions, and clustered damage in DNA films by $$alpha$$-radiation

Yokoya, Akinari; Cunniffe, S. M. T.*; Stevens, D. L.*; O'Neill, P.*

Journal of Physical Chemistry B, 107(3), p.832 - 837, 2003/01

 Times Cited Count:26 Percentile:55.77(Chemistry, Physical)

no abstracts in English

Journal Articles

Thymine glycol and 8-oxoguanine lesioned DNA-structural and energetical changes as onset of enzymatic recognition and repair; Large scale MD simulations of biomolecules

Pinak, M.; Nemoto, Toshiyuki*

Proceedings of International Conference on Supercomputing in Nuclear Applications (SNA 2003) (CD-ROM), 15 Pages, 2003/00

The molecular dynamics (MD) studies of oxidative lesions on DNA molecules are presented with respect to the proper recognition of lesions by their respective repair enzymes. The recognition of lesion and the formation of stable DNA-enzyme complex are necessary conditions for the onset of the enzymatic repair process. Two DNA lesions, thymine glycol and 8-oxoguanine were subjected to the MD simulations for several hundreds picoseconds using MD simulation codes AMBER 5.0 and AMBER 7.0. Amber was changed and partly vectorized to be able to handle this large systems. Simulations were performed on FUJITSU VPP5000/64 vector/parallel type, the HITACHI SR8000 and FUJITSU PRIMEPOWER parallel types supercomputers.

Journal Articles

Modelling the effect of incorporated halogenated pyrimidine on radiation-induced DNA strand breaks

Watanabe, Ritsuko; Nikjoo, H.*

International Journal of Radiation Biology, 78(11), p.953 - 966, 2002/11

 Times Cited Count:38 Percentile:89.62(Biology)

Incorporation of halogenated pyrimidines, iodo- and bromo-deoxyuridines (HP), into DNA is known to sensitize cells to radiation. The aim of this study is to estimate the enhancement of DNA strand break induced by low LET radiation in the presence of HP and examine source, complexity and clustering properties of damage that could provide correlation between DNA damage and lethality. Monte Carlo track structure methods were used to model the induction of strand breakage by X-ray photons. As a result, the increase of strand breaks due to Br/IdU incorporation could be explained by the mechanism of uracilyl radical production originated from e-aq and direct hits on bases. The significant contribution of electron migration along DNA within limited distance is shown. It is also shown that the incorporation of Br/IdU causes a spectral shift towards greater complexity of clustered DNA damage. Further, it has been supported that DSB is responsible for radiation-induced cell killing.

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