Initialising ...
Initialising ...
Initialising ...
Initialising ...
Initialising ...
Initialising ...
Initialising ...
Matsuya, Yusuke; Yoshii, Yuji*; Kusumoto, Tamon*; Akamatsu, Ken*; Hirata, Yuho; Sato, Tatsuhiko; Kai, Takeshi
Physics in Medicine & Biology, 19 Pages, 2023/00
Times Cited Count：0 Percentile：0.05(Engineering, Biomedical)Time-dependent yields of chemical products resulted in water radiolysis play a great role in evaluating DNA damage response after exposure to ionizing radiation. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo simulation code for radiation transport, which allows to determine several atomic interactions such as ionizations and electronic excitations as physical stage. However, a chemical code for simulating products of water radiolysis does not exist in the PHITS package. Here, we developed a chemical simulation code dedicated for the PHITS code, hereafter called PHITS-Chem code, which enables calculating G values of water radiolysis species (OH radical, e
, H
, HO etc) by electron beams. The estimated G values during 1 
s are in agreement with the experimental ones and other simulations. This PHITS-Chem code enables simulating the dynamics in the presence of OH radical scavenger, and is useful for evaluating contributions of direct and indirect effects on DNA damage induction. This code will be included and be available in the future version of PHITS.
Matsuya, Yusuke; Nakano, Toshiaki*; Kai, Takeshi; Shikazono, Naoya*; Akamatsu, Ken*; Yoshii, Yuji*; Sato, Tatsuhiko
International Journal of Molecular Sciences (Internet), 21(5), p.1701_1 - 1701_13, 2020/03
Times Cited Count：14 Percentile：64.54(Biochemistry & Molecular Biology)Among various DNA damage induced after irradiation, clustered damage composed of at least two vicinal lesions within from 10 to 20 base pairs is recognized as fatal damage to human tissue. Such clustered damage yields have been evaluated by means of computational approaches; however, the simulation validity has not been sufficiently made yet. Meanwhile, the experimental technique to detect clustered DNA damage has been evolved in the recent decades, so both approaches with simulation and experiment get used to be available for investigating clustered damage recently. In this study, we have developed a simple model for estimating clustered damage yield based on the spatial density of ionization and electronic excitation events obtained by the PHITS code, and compared the computational results to the experimental clustered damage coupled with base damage (BD) measured by gel electrophoresis and atomic force microscopy. The computational results agreed well with experimental fractions of clustered damage of strand breaks (SB) and BD, when the yield ratio of BD/SSB is assumed to be 1.3. From the comparison of complex DNA double-strand break coupled with BDs between simulation and experimental data, it was suggested that aggregation degree of the events along electron track reflects the complexity of DNA damage. The resent simulation enables to quantify the type of clustered damage which cannot be measured in in vitro experiment, which succeeded in interpreting the experimental detection efficiency for clustered BD.
Akamatsu, Ken; Shikazono, Naoya; Saito, Takeshi*
Radiation Research, 183(1), p.105 - 113, 2015/01
Times Cited Count：19 Percentile：64.42(Biology)Clustered DNA damage is considered an important factor in determining the biological consequences of ionizing radiation. We here succeeded in estimating the localization of abasic sites (APs) in DNA irradiated with ionizing radiation using fluorescence resonance energy transfer (FRET) without any involvement of repair enzyme functions. A linearized plasmid was irradiated with 
Co 
-rays, the 
He
beam, and the 
C
beam in the solid state. A donor or acceptor fluorescent probe with a nucleophilic O-amino group was used to label APs. The results showed that the C beam likely produced close APs within a track. On the other hand, E values of Co -rays and the He beam were less than those of the C beam, increased with increasing AP density, and were slightly greater than those of randomly distributed APs.
processing of clustered DNA damageShikazono, Naoya; Akamatsu, Ken; Takahashi, Momoko*; Noguchi, Miho; Urushibara, Ayumi; O'Neill, P.*; Yokoya, Akinari
Mutation Research; Fundamental and Molecular Mechanisms of Mutagenesis, 749(1-2), p.9 - 15, 2013/09
Times Cited Count：12 Percentile：36.83(Biotechnology & Applied Microbiology)We examined the biological consequences of bi-stranded clustered damage sites, consisting of a combination of DNA lesions using a bacterial plasmid-based assay. The transformation efficiencies were significantly lower for the bi-stranded clustered GAP/AP lesions than for either a single GAP or a single AP site. When the two lesions were separated by 10-20 bp, the transformation efficiencies were comparable with those of the single lesions. This recovery of transformation efficiency for separated lesions requires DNA polymerase I (Pol I) activity. Analogously, the mutation frequency was enhanced in a bi-stranded cluster containing a GAP and an 8-oxoG, and Pol I was found to play an important role in minimising mutations induced as a result of clustered lesions. These results indicate that the biological consequences of clustered DNA damage strongly depend on Pol I activity.
Akamatsu, Ken
Applied Radiation and Isotopes, 74, p.144 - 151, 2013/04
Times Cited Count：3 Percentile：25.73(Chemistry, Inorganic & Nuclear)Effects of lipid compositions and the content ratios on the membrane permeability of liposome have been investigated using soft X-rays as ionizing radiation (IR) sources. Three-component liposome constituted from an unsaturated phosphatidyl choline (PC), a saturated PC, and cholesterol was selected in a series of the study. As the results, following characteristics of IR-sensitive liposome were discovered: (1) A PC with bis-allylic hydrogen is essential as a component of unsaturated PC., (2) Dilinoleoyl PC (DLOPC) is optimal as a component of unsaturated PC., (3) Either distearoyl PC (DSPC) or dipalmitoyl PC (DPPC) is optimal as a component of saturated PC., (4) Lower dose- rate makes the liposome more IR-sensitive., (5) Lower concentration of liposome makes the liposome more IR-sensitive., (6) There is a region for optimal DLOPC content ratio for the IR-sensitive liposome around 5 
20 mol%., and (7) There is a region for optimal cholesterol content ratio for preparing a stable liposome around 30 60 mol%. These fundamental laws for IR-sensitive liposome will contribute to understanding of biomembrane damage by IRs and developing a new-conceptual pharmaceutical available in radiotherapies.
Akamatsu, Ken; Shikazono, Naoya
Analytical Biochemistry, 433(2), p.171 - 180, 2013/02
Times Cited Count：5 Percentile：18.12(Biochemical Research Methods)Akamatsu, Ken
Hoshasen Seibutsu Kenkyu, 46(2), p.87 - 92, 2011/06
"Health counseling hot line" concerning the radiation and the radiological consequence was established in the Ministry of Education, Culture, Sports, Science and Technology along with the nuclear disaster due to the East Japan great earthquake. The author and some other staffs of Japan Atomic Energy Agency were consulted by a lot of Japanese clients as a temporary risk-communicator. The concern for nuclear power and the radioactivity and the radiation has spread not only domestically but also all over the world by this disastrous. In this paper, the author discusses how we communicate with a client worrying about radiation risks based on his experiences.
Akamatsu, Ken
Hoshasen Kagaku (Internet), (89), p.3 - 8, 2010/03
I have been considering how to clarify chemical difference in DNA damage spectrum among radiation qualities. In order to confront the problem, it should be necessary to develop new-conceptual analytical methods for damaged DNA by ionizing radiation. In this report, following to the explanation of overall background of upstream of radiation biology, brief history of the analytical chemistry with problems, a few analytical trials to discover characteristics of radiation qualities are demonstrated. The present efforts against the problems are discovering difference in strand- break termini between high- and low- LET radiation.
Akamatsu, Ken
Radiation Physics and Chemistry, 78(12), p.1179 - 1183, 2009/12
Times Cited Count：7 Percentile：45.28(Chemistry, Physical)An ionizing radiation-sensitive liposome has been developed aiming for irradiation site-specific controlled release of an anticancer agent from liposomes accumulated at tumor. As the first step of the study, X-ray-sensitive liposome has been constructed, consisting of an unsaturated phosphatidyl choline (PC), a saturated PC, and cholesterol. The radiation sensitivity was estimated by measuring release rate of a fluorophore, calcein, through the lipid bilayer. As a result, the following characteristics of X-ray-sensitive liposomes were discovered: (1) A PC with bis-allylic hydrogen is an essential component of unsaturated PC, (2) Dilinoleoyl PC (DLOPC) is the most favorable component of unsaturated PC, (3) A lower dose rate makes the liposome more X-ray-sensitive. In this presentation, we will discuss radiation chemical mechanism of the ionizing radiation-sensitive liposome, and their pharmaceutical applications for radiation therapy such as boron neutron capture therapy.
-ray irradiation of organic extractants for the separation of minor actinides by the tandem acceleratorSugo, Yumi; Akamatsu, Ken; Hase, Yoshihiro; Taguchi, Mitsumasa; Sasaki, Yuji; Hirota, Koichi; Kimura, Takaumi
JAEA-Conf 2008-012, p.127 - 129, 2009/03
no abstracts in English
Yokoya, Akinari; Fujii, Kentaro; Shikazono, Naoya; Akamatsu, Ken; Urushibara, Ayumi; Watanabe, Ritsuko
International Journal of Radiation Biology, 84(12), p.1069 - 1081, 2008/12
Times Cited Count：12 Percentile：61.74(Biology)The role of Auger effect in inducing DNA damage has been studied using soft X-ray irradiation, which mainly cause photoelectric effect of DNA constituent atoms. As a consequence of Auger decay process, ejected low energy photo- or Auger-electrons might impact on proximately chemical group in the molecule. These highly localized collision events are expected to lead to a clustered DNA damage site within a few nano-meter. We have revealed that soft X-ray (60 keV) induced lesions visualized by the enzymatic probes show much higher yields than those induced by low LET -ray irradiation, and the yields decreased with decreasing soft X-ray energy (below a few keV). These results indicate that the complexity of damage site strongly depends on photo- or Auger electron range. The recent progress that has been made in the study of the process of DNA-radicals as precursors using an EPR apparatus combined with a synchrotron soft X-ray source is also presented.
Akamatsu, Ken; Fujii, Kentaro; Yokoya, Akinari
International Journal of Radiation Biology, 84(12), p.1082 - 1092, 2008/12
Times Cited Count：0 Percentile：0.01(Biology)The aim of this study is to clarify the difference of DNA damage induced by USX from that by Co-60 -rays. We have recently attended to unaltered base release, strand break terminus and base lesion, focusing on the effect of nitrogen and oxygen K-shell electron ionization. The yields of unaltered bases released were determined by HPLC. To quantify and characterize the strand break termini, the digestion rates of the irradiated DNA pretreated with or without calf intestinal alkaline phosphatase by snake venom phosphodiesterase (SVPD) were measured. This experimental method revealed that the production of the termini, which can not be digested by SVPD, were predominant in comparison with that of SVPD- digestive ones, e.g., with 3'OH, in both USX and -rays. Furthermore, piperidine-treated irradiated DNA was also analyzed by the same method above to quantify piperidine-labile base lesions.
Yokoya, Akinari; Shikazono, Naoya; Fujii, Kentaro; Urushibara, Ayumi; Akamatsu, Ken; Watanabe, Ritsuko
Radiation Physics and Chemistry, 77(10-12), p.1280 - 1285, 2008/10
Times Cited Count：53 Percentile：94.95(Chemistry, Physical)Ionizing radiation induces a variety of damages in cellular DNA, which is thought to be the critical target of biological effects of radiation, by both direct energy deposition on DNA (direct effect) and reactions with diffusible water radicals (indirect effect). One of the goals of our study is to clarify the nature of DNA damage induced by direct effect. The yields of single- and double-strand breaks, base lesions and clustered damage induced in a plasmid DNA were measured after exposing to various kinds of radiation (ion particles; 20 to 500 keV/ , photons; 0.4 keV to 1.3 MeV). Base excision repair enzymes were used to detect the oxidative base lesions. In order to obtain more detailed insights into the physicochemical mechanism of DNA damage induction, short-lived base radicals by applying an EPR spectrometer at a synchrotron ultrasoft X-ray beamline. Experimental evidences obtained by these methods will be discussed in comparison with the previous plasmid data.
Akamatsu, Ken
New Research on DNA damage, p.237 - 253, 2008/00
We have developed new-conceptual analytical methodology to estimate the DNA damage spectrum on natural DNA without radioisotope and fluorescent labeling. DNA damage is generally classified into two categories. one is "strand break", the other is "nucleobase lesion". There are two kinds of termini in the strand break pattern: the termini with or without phosphate. We have developed the protocols to quantify (1) 3'termini without phosphate, (2) 3'termini with phosphate, and (3) nucleobase lesions. An enzyme, phosphodiestrase I (snake venom phosphodiesterase (SVPD)), can recognize a 3'terminus without phosphate followed by production of DNA monomers (2'-deoxynucleoside-5'-phosphate) sequentially from the 3'terminus (3'
5'exonuclease function). Then, the yield of site (1) can be quantified since the amount of the DNA monomers produced during incubation for a given period is proportional to that of site (1). In addition, pre-treatment of irradiated DNA by another enzyme, calf intestine alkaline phosphatase (CIAP) enables site (2) to be recognized by SVPD, because CIAP removes phosphate at site (2) to convert into 3'OH terminus categorized in site (1). Furthermore, pre-treatment of irradiated DNA by a chemical, piperidine, can covert several electron-withdrawing nucleobase lesions into site (2), which can become recognizable by SVPD after CIAP pre-treatment as mentioned obove. As a result, in case of Co -irradiated dry DNA, the yields of total 3'termini, 3'termini without phosphate, 3'termini with phosphate, and piperidine-labile nucleobase lesions, are estimated to be 0.102, 0.024, 0.078, and 0.084, respectively. The de novo analytical protocol is unique in the idea itself, and future analyses based on the methodology will elucidate unknown DNA damage spectrum using a variety of combinations of enzymes.
Akamatsu, Ken
Analytical Biochemistry, 362(2), p.229 - 235, 2007/03
Times Cited Count：4 Percentile：13.59(Biochemical Research Methods)We have developed a de novo methodology to characterize radiation damage in DNA. An enzyme system consisting of snake venom phosphodiesterase (SVPD) and calf intestine alkaline phosphatase (CIAP) was used to examine the 3'termini of strand break sites. In this study, we hypothesized that the strand-break termini can be divided into two categories. The apparent radiation-chemical yield (G-value) can be estimated using the level of intact 2'-deoxynucleotides produced during a 15-min incubation with SVPD. The G-value for total strand breaks in dried DNA irradiated with Co -rays was estimated to be 0.1 micromol/J. Moreover, the G-values of CIAP-dependent and CIAP-independent SVPD sites were estimated to be 0.078 and 0.024 micromol/J, respectively. These values suggest that 3'-phosphate termini are more likely to be produced than 3'termini without phosphate.
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.
" observation of guanine radicals induced by ultrasoft X-ray irradiation around the K-edge regions of nitrogen and oxygenYokoya, Akinari; Akamatsu, Ken; Fujii, Kentaro; Ukai, Masatoshi*
International Journal of Radiation Biology, 80(11-12), p.833 - 839, 2004/12
Times Cited Count：8 Percentile：48.81(Biology)no abstracts in English
-ribose by irradiation with 0.6 keV electrons and by 0.5 keV ultrasoft X-raysFujii, Kentaro; Akamatsu, Ken; Yokoya, Akinari
International Journal of Radiation Biology, 80(11-12), p.909 - 914, 2004/11
Times Cited Count：9 Percentile：52.68(Biology)no abstracts in English
Akamatsu, Ken; Fujii, Kentaro; Yokoya, Akinari
International Journal of Radiation Biology, 80(11-12), p.849 - 853, 2004/11
Times Cited Count：11 Percentile：58.51(Biology)The productions of stable/unstable thymine radicals produced by monochromatic ultrasoft X (USX)- or Co -rays were studied using EPR spectroscopy. EPR experiment of thymine was performed using a newly developed X-band EPR device installed in a JAERI soft X-ray beamline (BL23SU) in SPring-8. The sample pellet was irradiated with USX photons at a microwave in a vacuum chamber. EPR measurements of a thymine powder pellet irradiated with USX around 500 eV at 77 K and RT. As a reference, Co g-irradiation to the pellet was also performed at RT. As the results, following three findings are obtained: (1) An unstable radical appearing only in situ USX-irradiation is observed. And the radical is clearly distinguished with other stable radicals remaining after irradiation. (2) The signal of the unstable radical is a strong singlet, which vanishes after irradiation immediately.
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 Co -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.
