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Sato, Tatsuhiko; Yasuda, Hiroshi*; Niita, Koji*; Endo, Akira; Sihver, L.*
no journal, ,
We performed Monte Carlo simulations for estimating the terrestrial cosmic-ray spectra using our developing code PHITS. Excellent agreements were observed between the calculated and measured spectra for almost all particles that contribute to the cosmic-ray doses for a wide altitude range even at the sea level. Based on a comprehensive analysis of the simulation results, we proposed analytical functions that can predict the cosmic-ray spectra for anywhere in the world except for the locations with altitudes over 20 km. The functions coupled with the fluence to dose conversion coefficients enable us to calculate the cosmic-ray dose rates in a short computational time. This analytical model will be incorporated into the Japanese Internet System for Calculation of Aviation Route Doses JISCARD.
Yasuda, Hiroshi*; Sato, Tatsuhiko; Takada, Masashi*; Nakamura, Takashi*
no journal, ,
It is important to know accurately energy spectra of energetic neutrons (
10MeV) for radiological protection of aircraft and spacecraft crew. We thus try to develop a portable neutron detector which can automatically measure energetic cosmic neutrons in the high-energy range separately from charged particles and 
rays. For testing the feasibility of our concept, experiments of cosmic radiation measurements were performed in a jet aircraft using various detectors (scintillation counters, dose-equivalent counters and an ionization chamber). The measured data were compared to model calculations using the PHITS-based analytical code.
Funayama, Tomoo; Wada, Seiichi*; Kakizaki, Takehiko; Hamada, Nobuyuki*; Yokota, Yuichiro; Sakashita, Tetsuya; Kobayashi, Yasuhiko
no journal, ,
To explore a mechanism underlying bystander growth inhibition induced by heavy-ion microbeam radiation, we focused on DNA double strand breaks (DSBs), which are known as a trigger of various radiation response of direct hit cells. We irradiated by 5 count of 
Ar ion microbeam (11.5 MeV/u, LET=1260 keV/
m), and induction of DSBs were visualized by immunostaining of phospohlylated histone H2AX (H2AX), which is known as a molecular marker of DSBs. The samples with the postincubation time longer than 30 minutes showed increased frequency of H2AX positive cells compared with medium-irradiated control sample in a range of 3-4%. This result suggested that the heavy ion irradiation induced bystander effect on the phosphorylation of histone H2AX in CHO-K1 cells. As H2AX is a molecular marker of DSBs, the result suggests that heavy-ion radiation induces DSBs not only on direct hit cells, but on bystander cells.
Shikazono, Naoya; Pearson, C.*; Thacker, J.*; O'Neill, P.*
no journal, ,
Clustered DNA damage induced by a single radiation track is a unique feature of ionizing radiation. Recent 
studies have shown that the repair of lesions within clusters may be retarded, but less is known about the processing and the mutagenic effects of such clustered damage in vivo. Using a bacterial plasmid-based assay, we have investigated the mutagenic potential of bistranded clustered damage sites which consist of 8-oxo-7,8-dihydroguanine (8-oxoG) and dihydrothymine (DHT) at defined separations. We found a significantly higher mutation frequency for the clustered DHT + 8-oxoG lesions than that for either a single 8-oxoG or a single DHT in wild-type and in glycosylase-deficient strains of 
. From these results and similarities with the mutability of respective 8-oxoG + AP clusters, it is suggested that removal of 8-oxoG within clustered damage site is retarded, probably reflecting the preferential excision of DHT initially. For a certain fraction of clusters, 8-oxoG may be initially removed from the cluster. To gain further insights on the processing of the DHT + 8-oxoG cluster, several potential intermediates after 8-oxoG removal were assessed for their mutability. For instance, DHT + AP or DHT + Gap containing cluster, but not AP + AP or Gap +AP clusters, has a relatively low mutation frequency. Further, AP + AP or Gap + AP cluster had a reduced transformation efficiency. These results led us to suggest that, when either 8-oxoG or DHT is initially excised from a cluster containing 8-oxoG and DHT, the base remaining within the resulting damage will not be further converted to an AP site or to a single strand break 
.
Noguchi, Miho; Hirayama, Ryoichi*; Okayasu, Ryuichi*
no journal, ,
We investigated radiosensitization effect and its mechanism of Hsp90 inhibitor 17-AAG in human tumor cell lines irradiated with high LET carbon ions. Human tumor cell lines, DU145 derived from prostate carcinoma and normal human fibroblasts HFL III were incubated for 24 h in the presence of 17-AAG at concentration of 100nM. The cells were then irradiated with carbon ions (290MeV/nucleon, LET70keV/um) and several biological endpoints were compared. Cellular radiation sensitivity was determined by clonogenic assay and DNA double strand break (DSB) repair kinetics were examined by constant field gel electrophoresis. DU145 cells showed an increase in carbon ions-induced cell death when pre-treated with 17-AAG. The radiosensitivity enhancement ratios measured at a survival rate of 10% were 2.13 for DU145 cells. In contrast to the tumor cell lines, normal human fibroblasts with carbon irradiation showed no radiosensitization with 17-AAG pre-treatment. Our constant field gel electrophoresis studies indicated that 17-AAG had almost no effect on carbon ion-induced DSB repair in DU145 cells. On the other hand, radiation induced Rad51 foci formation showed different kinetics between the carbon ion alone and the combined treatment with 17-AAG and carbon ions in DU145 cells. Our findings suggest that mechanisms other than inhibition of DSB repair could be involved with the radiosensitization by 17-AAG in tumor cells irradiated with carbon ions. However, limited inhibition of homologous recombination by this agent may still be a possibility.
Fujii, Kentaro; Yokoya, Akinari; Shikazono, Naoya
no journal, ,
To investigate the direct effect of constituent atoms on DNA damage, dry plasmid DNA (pUC18) films were irradiated with synchrotron monochromatic ultrasoft X-rays. Four photon energies, 270, 380, 435, and 560eV, a value below the carbon K-edge, below and above the nitrogen K-edge, and above the oxygen K-edge, respectively, were chosen for the irradiation experiments. Irradiated plasmid DNA was analyzed by agarose gel electrophoresis and the yields of strand breaks were determined by measuring the band intensities of the separated closed circular, open circular and linear forms of the plasmid DNA. The yields of base lesions and clustered damage site including at least one base lesion were determined by the post-irradiation-treatment of the DNA with enzymatic probes (Fpg and Endo III) which convert base lesions into detectable strand breaks.
raysYokota, Yuichiro; Wada, Seiichi*; Tanaka, Atsushi; Narumi, Issei
no journal, ,
There is an interesting but still-unsolved issue in radiation biology: a part of higher plants show high radiation tolerance. In this study, we investigated the rejoining ability of DNA double-strand breaks (DSBs) in tobacco cells by pulsed-field gel electrophoresis (PFGE) assay and clastogenic effects by micronucleus (MN) assay. In the PFGE assay, an equal level of DSB rejoining ability was observed between tobacco cells and Chinese hamster cells. We monitored MN formation in tobacco cells and found that the rate (cells having at least one MN per observed cells) reached the maximum at 2 day-post-irradiation (DPI). The MN formation rate at 2 DPI increased with ray dose and was 40 % at LD
(27.4 Gy). In mammalian cells irradiated with LD of rays, MN formation rates are generally 30 % or less. In summary, tobacco cells are permissive to clastogenic effects of ionizing radiation, and this appears to contribute the radiation tolerance.
Akamatsu, Ken; Wada, Seiichi*; Kobayashi, Yasuhiko
no journal, ,
We have developed new methodology to characterize radiation damage in DNA. An enzyme system consisting of the 3' to 5'exonuclease 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:CIAP-independent SVPD sites and CIAP-dependent SVPD sites. The former consists of strand-break termini that can directly be recognized and digested by SVPD without CIAP pretreatment, whereas the latter includes the termini that cannot be digested by SVPD without CIAP pretreatment. As the results, the G-value for total strand breaks in fully 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.
Taguchi, Mitsumasa; Kimura, Atsushi; Baldacchino, G.*; Katsumura, Yosuke*; Hirota, Koichi
no journal, ,
Heavy ions give unique irradiation effects on target materials. Reactions in water under heavy ion irradiation are mainly induced by OH (hydroxyl) radicals. OH radicals yields have been investigated by the (1) product analysis and (2) pulse radiolysis methods. (1) Aqueous phenol solutions were irradiated with He, C and Ne ions. The yields of the OH radicals were estimated by analyzing the yields of the irradiation products of phenol. The yields of the OH radicals increased with the specific energy, but decreased with both the mass of each ion and elapsed time. (2) Transient absorption measurement system was developed for the direct observation of radical behaviors in water under heavy ion irradiation. A small absorbance change less than 10
was recorded. The transient absorbance of (SCN)
formed by the reaction of OH radicals with SCN in aqueous KSCN solution was observed under pulsed C ion irradiation.
Hamada, Nobuyuki*; Hara, Takamitsu*; Sakashita, Tetsuya; Funayama, Tomoo; Sora, Sakura; Kobayashi, Yasuhiko
no journal, ,