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
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.
Hata, Kuniki; Urushibara, Ayumi*; Yamashita, Shinichi*; Lin, M.*; Muroya, Yusa*; Shikazono, Naoya; Yokoya, Akinari; Fu, H.*; Katsumura, Yosuke*
Journal of Radiation Research, 56(1), p.59 - 66, 2015/01
Akamatsu, Ken; Shikazono, Naoya; Saito, Takeshi*
Radiation Research, 183(1), p.105 - 113, 2015/01
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.
Ledingham, K.*; Bolton, P. R.*; Shikazono, Naoya; Ma, C.-M.*
Applied Sciences (Internet), 4(3), p.402 - 443, 2014/09
Shiraishi, Iyo; Suzuki, Masao*; Shikazono, Naoya; Fujii, Kentaro; Yokoya, Akinari
Journal of Radiation Research, 55(Suppl.1), p.i92 - i93, 2014/03
Shikazono, 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
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.
Hata, Kuniki; Urushibara, Ayumi; Yamashita, Shinichi; Shikazono, Naoya; Yokoya, Akinari; Katsumura, Yosuke*
Biochemical and Biophysical Research Communications, 434(2), p.341 - 345, 2013/05
Akamatsu, Ken; Shikazono, Naoya
Analytical Biochemistry, 433(2), p.171 - 180, 2013/02
Ushigome, Takeshi*; Shikazono, Naoya; Fujii, Kentaro; Watanabe, Ritsuko; Suzuki, Masao*; Tsuruoka, Chizuru*; Tauchi, Hiroshi*; Yokoya, Akinari
Radiation Research, 177(5), p.614 - 627, 2012/05
The yield of DNA damage produced in fully hydrated plasmid DNA films has been investigated to determine the linear energy transfer (LET) dependence of damage induction. The yield of single strand breaks (SSBs) with increasing LET levels of He, C and Ne ions. On the other hand, the yields of prompt double strand breaks (DSBs) increased with increasing LET. SSBs were additionally induced by treatment with base excision repair proteins, glycosylases, indicating that base lesions are produced in the hydrated DNA. This result shows that nucleobase lesions are produced via both chemical reactions with diffusible water radicals and direct energy deposition onto DNA or the hydrated layer. The yield of SSBs or DSBs observed by enzymatic treatment notably decreased with increasing LET. These results indicated that higher LET ions preferentially produce a complex type of damage that might compromise the activities of the proteins used in this study.
Noguchi, Miho; Urushibara, Ayumi; Yokoya, Akinari; O'Neill, P.*; Shikazono, Naoya
Mutation Research; Fundamental and Molecular Mechanisms of Mutagenesis, 732(1-2), p.34 - 42, 2012/04
The effect of a single strand break associated with base lesion(s) in vivo remains largely unknown. In the present study we determined the mutagenicities of two- and three-lesion clustered damage sites containing a 1-nucleotide gap (GAP) and 8-oxo-7,8-dihydroguanine(s) (8-oxoG(s)). The mutation frequencies (MFs) of bi-stranded two-lesion clusters (GAP/8-oxoG), especially in mutY-deficient strains, were high and were similar to those for bi-stranded clusters with 8-oxoG and base lesions/AP sites, suggesting that the GAP is processed with an efficiency similar to the efficiency of processing a base lesion or an AP site within a cluster. The MFs of tandem two-lesion clusters comprised of a GAP and an 8-oxoG were comparable to or less than the MF of a single 8-oxoG. The mutagenic potential of three-lesion clusters, which were comprised of a tandem lesion (a GAP and an 8-oxoG) and an opposing single 8-oxoG, was higher than that of a single 8-oxoG, but was no more than that of a bi-stranded 8-oxoGs. We suggest that incorporation of a nucleotide opposite 8-oxoG is less mutagenic when a GAP is present in a cluster than when a GAP is absent. Our observations indicate that the repair of a GAP is retarded by an opposing 8-oxoG, but not by a tandem 8-oxoG, and that the extent of GAP repair determines the biological consequences.
Yokoya, Akinari; Shikazono, Naoya; Fujii, Kentaro; Noguchi, Miho; Urushibara, Ayumi
Radiation Protection Dosimetry, 143(2-4), p.219 - 225, 2011/02
Multiple single-strand breaks (m-SSBs), which are predicted to be preferentially induced by high LET radiation, would be underestimated if one uses the conventional method using plasmid DNA, because m-SSBs will not cause additionally conformational changes if they are on the same or on the opposite strand but separated each other sufficiently so as not to induce a double strand break. In order to observe the invisible m-SSBs, we have developed a novel technique using DNA denaturation. The m-SSBs arising in both strands of DNA are revealed as molecular size change in single strand DNA (SS-DNA) by gel electrophoresis. We have applied this method to the X- and He ion irradiated sample of hydrated pUC18 plasmid DNA. A half of SS-DNA population remains as intact within the experimental resolution ( 140 bases) for both irradiations. Contrary to our initial expectation, these results indicate that SSBs are not multiply induced over 140 bp even by high-LET irradiation.
Shikazono, Naoya; Yokoya, Akinari; Urushibara, Ayumi; Noguchi, Miho; Fujii, Kentaro
Radiation Protection Dosimetry, 143(2-4), p.181 - 185, 2011/02
Yokoya, Akinari; Fujii, Kentaro; Shikazono, Naoya; Ukai, Masatoshi*
Charged Particle and Photon Interactions with Matter; Recent Advances, Applications, and Interfaces, p.543 - 574, 2010/12
This review is one of the chapters of "Charged Particle and Photon Interactions with Matter; Recent Advances, Applications, and Interfaces". In this review we will introduce recent advances in spectroscopic study of DNA damage induced by ionizing radiation using synchrotron radiation and ion particles. Further, studies of susceptibility of DNA damage to enzymatic repair-processes revealed by biochemical techniques, as well as mutation assay for E. coli cells, will also be described and discussed by comparing with previous simulation data.
Fu, H. Y.*; Lin, M.; Katsumura, Yosuke*; Yokoya, Akinari; Hata, Kuniki; Muroya, Yusa*; Fujii, Kentaro; Shikazono, Naoya
Acta Biochimica et Biophysica Sinica, 42(7), p.489 - 495, 2010/07
Silybin (SLB) and similar analogues, namely, hesperetin (HESP), naringenin (NAN) and naringin (NAR), are believed to be active constituents of natural flavonoids that have been reported as chemopreventive agents for certain cancers. Moreover, SLB and analogues have been determined to fast repair DNA bases from oxidative damage by pulse radiolysis techniques. The present study was designed to evaluate the protective effects of SLB and analogues on soft X-ray-induced damage to plasmid DNA in vitro. Among the compounds tested, HESP and SLB were the most effective in preventing X-ray-induced formation of DNA single-strand breaks (SSB). A comparison of these results with other experiments showed that the ability of SLB and analogues to inhibit DNA damage in vitro correlated with the ability of the compounds to scavenge free radicals. Our work revealed that natural flavonoids, SLB and analogues may be used as potent protectors against radiation damage.
Tanaka, Atsushi; Shikazono, Naoya; Hase, Yoshihiro
Journal of Radiation Research, 51(3), p.223 - 233, 2010/05
Fujii, Kentaro; Shikazono, Naoya; Yokoya, Akinari
Journal of Physical Chemistry B, 113(49), p.16007 - 16015, 2009/11
In order to verify the possibility of selective damage induction in DNA, the yields of base lesions as well as strand breaks have been measured in dry plasmid DNA films irradiated with highly monochromatized soft X-rays in the energy region of 270-760 eV, which includes the carbon, nitrogen and oxygen K-edges. Our results strongly suggest that (1) the K-shell ionization of oxygen in both the nucleobases as well as in other parts of DNA and in the hydrating water molecules bound to DNA, but not the K-shell ionization of nitrogen in the nucleobases, most likely contributes to the induction of nucleobase lesions, and (2) migration of electrons and holes are involved differentially in the production of each type of DNA lesion. These results could potentially lead to new methods for selective induction of specific types of DNA damage through tuning the energy of soft X-rays.
Shikazono, Naoya; O'Neill, P.*
Mutation Research; Fundamental and Molecular Mechanisms of Mutagenesis, 669(1-2), p.162 - 168, 2009/11
Fu, H. Y.*; Lin, M.; Muroya, Yusa*; Hata, Kuniki; Katsumura, Yosuke; Yokoya, Akinari; Shikazono, Naoya; Hatano, Yoshihiko
Free Radical Research, 43(9), p.887 - 897, 2009/09
Bellon, S.*; Shikazono, Naoya; Cunniffe, S. M. T.*; Lomax, M.*; O'Neill, P.*
Nucleic Acids Research, 37(13), p.4430 - 4440, 2009/07
Sakamoto, Ayako; Lan, V. T. T.*; Puripunyavanich, V.*; Hase, Yoshihiro; Yokota, Yuichiro; Shikazono, Naoya; Nakagawa, Mayu*; Narumi, Issei; Tanaka, Atsushi
Plant Journal, 60(3), p.509 - 517, 2009/07
no abstracts in English