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Journal Articles

Microdosimetric modeling of relative biological effectiveness for skin reactions; Possible linkage between in vitro and in vivo data

Sato, Tatsuhiko; Matsuya, Yusuke; Hamada, Nobuyuki*

International Journal of Radiation Oncology, Biology, Physics, 10 Pages, 2022/05

The microdosimetric kinetic model, which was originally developed for estimating cell surviving fractions for various radiations, was improved to be capable of estimating the mean and uncertainty of RBE for skin reactions. The parameter used in the model was independently determined from in vitro measurements of dermal cell survival and in vivo measurements of skin reactions taken from 8 and 23 papers, respectively. Our model quantitatively revealed that RBE for skin reactions tend to be higher than that for dermal cell survival. RBE of various mono-energetic radiations calculated from this model confirmed that the past evaluations made by ICRP and NCRP a few decades ago are still supported by recent experimental data. Conclusions: Our model can play important roles not only in medical physics for avoiding unnecessary skin reactions in particle therapy and BNCT but also in radiation protection for future decision making of the recommended RBE values.

Journal Articles

Track-structure modes in Particle and Heavy Ion Transport code System (PHITS); Application to radiobiological research

Matsuya, Yusuke; Kai, Takeshi; Sato, Tatsuhiko; Ogawa, Tatsuhiko; Hirata, Yuho; Yoshii, Yuji*; Parisi, A.*; Liamsuwan, T.*

International Journal of Radiation Biology, 98(2), p.148 - 157, 2022/02

When investigating radiation-induced biological effects, it is essential to perform detailed track-structure simulations explicitly by considering each atomic interaction in liquid water (which is equivalent to human tissues) at sub-cellular and DNA scales. The Particle and Heavy Ion Transport code System (PHITS) is a Monte Carlo code which can be used for track structure calculations by employing an original electron track-structure mode (etsmode) and the world-famous KURBUC algorithms (PHITS-KURBUC mode) for protons and carbon ions. In this study, the physical features (i.e., range, radial dose and microdosimetry) of these modes have been verified by comparing to the available experimental data and Monte Carlo simulation results reported in literature. In addition, applying the etsmode to radiobiological study, we estimated the yields of single-strand breaks (SSBs), double-strand breaks (DSBs) and complex DSBs, and evaluated the dependencies of DNA damage yields on incident electron energy. As a result, the simulations suggested that DNA damage types are intrinsically related with the spatial patterns of ionization and electronic excitations and that approximately 500 eV electron can cause much complex DSBs. In this paper, we show the development status of the PHITS track-structure modes and its application to radiobiological research, which would be expected to identify the underlying mechanisms of radiation effects based on physics.

Journal Articles

Implementation of simplified stochastic microdosimetric kinetic models into PHITS for application to radiation treatment planning

Sato, Tatsuhiko; Hashimoto, Shintaro; Inaniwa, Taku*; Takada, Kenta*; Kumada, Hiroaki*

International Journal of Radiation Biology, 97(10), p.1450 - 1460, 2021/10

 Times Cited Count:0 Percentile:0.01(Biology)

The stochastic microdosimetric kinetic (SMK) model is one of the most sophisticated and precise models used in the estimation of the relative biological effectiveness of carbon-ion radiotherapy (CRT) and boron neutron capture therapy (BNCT). Through the introduction of Taylor expansion (TE) or fast Fourier transform (FFT), we developed two simplified SMK models and implemented them into the Particle and Heavy Ion Transport code System (PHITS). This study enables the instantaneous calculation of the equieffective dose for CRT and BNCT, considering their cellular-scale dose heterogeneities. Treatment-planning systems that use the improved PHITS as a dose-calculation engine are under development.

Journal Articles

Recent discussions toward regulatory implementation of the new occupational equivalent dose limit for the lens of the eye and related studies in Japan

Yokoyama, Sumi*; Hamada, Nobuyuki*; Tsujimura, Norio

International Journal of Radiation Biology, 95(8), p.1103 - 1112, 2019/08

 Times Cited Count:7 Percentile:75.7(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:25.63(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:6 Percentile:61.4(Biology)

Journal Articles

The Bystander cell-killing effect mediated by nitric oxide in normal human fibroblasts varies with irradiation dose but not with radiation quality

Yokota, Yuichiro; Funayama, Tomoo; Muto, Yasuko*; Ikeda, Hiroko; Kobayashi, Yasuhiko

International Journal of Radiation Biology, 91(5), p.383 - 388, 2015/05

 Times Cited Count:7 Percentile:60.95(Biology)

We investigated the dependence of the bystander cell-killing effect on radiation dose and quality, and related molecular mechanisms. Human fibroblasts were irradiated with $$gamma$$-rays or carbon ions and co-cultured with non-irradiated cells. Survival rates of non-irradiated cells decreased and nitrite concentrations in culture medium increased with increasing doses. Their dose responses were similar between $$gamma$$-rays and carbon ions. Treatment of the specific nitric oxide (NO) radical scavenger prevented reductions in survival rates of non-irradiated cells. Negative relationships were observed between survival rates and nitrite concentrations. From these results, it was concluded that the bystander cell-killing effect mediated by NO radicals in human fibroblasts depends on irradiation doses, but not on radiation quality. NO radical production appears to be an important determinant of $$gamma$$-ray- and carbon-ion-induced bystander effects.

Journal Articles

Genetic changes in progeny of bystander human fibroblasts after microbeam irradiation with X-rays, protons or carbon ions; The Relevance to cancer risk

Autsavapromporn, N.*; Plante, I.*; Liu, C.*; Konishi, Teruaki*; Usami, Noriko*; Funayama, Tomoo; Azzam, E.*; Murakami, Takeshi*; Suzuki, Masao*

International Journal of Radiation Biology, 91(1), p.62 - 70, 2015/01

 Times Cited Count:23 Percentile:93.53(Biology)

Radiation-induced bystander effects have important implications in radiotherapy. Their persistence in normal cells may contribute to risk of health hazards, including cancer. This study investigates the role of radiation quality and gap junction intercellular communication (GJIC) in the propagation of harmful effects in progeny of bystander cells. Confluent human skin fibroblasts were exposed to microbeam radiations with different linear energy transfer (LET) by which 0.036$$sim$$0.4% of the cells were directly targeted by radiation. Following 20 population doublings, the cells were harvested and assayed for micronucleus formation, gene mutation and protein oxidation. The results showed that expression of stressful effects in the progeny of bystander cells is dependent on LET.

Journal Articles

Development of a simulation method for dynamics of electrons ejected from DNA molecules irradiated with X-rays

Kai, Takeshi; Higuchi, Mariko; Fujii, Kentaro; Watanabe, Ritsuko; Yokoya, Akinari

International Journal of Radiation Biology, 88(12), p.928 - 932, 2012/12

 Times Cited Count:1 Percentile:13.84(Biology)

Journal Articles

Observation of cleavage in DNA and nucleotides following oxygen $$K$$-shell ionization by measuring X-ray absorption near edge structure

Fujii, Kentaro; Fukuda, Yoshihiro; Yokoya, Akinari

International Journal of Radiation Biology, 88(12), p.888 - 894, 2012/12

 Times Cited Count:3 Percentile:28.72(Biology)

Journal Articles

Lifetime of the unpaired electron species in calf thymus DNA thin films induced by nitrogen and oxygen K-shell photoabsorption

Oka, Toshitaka; Yokoya, Akinari; Fujii, Kentaro

International Journal of Radiation Biology, 88(12), p.884 - 887, 2012/12

 Times Cited Count:3 Percentile:28.72(Biology)

no abstracts in English

Journal Articles

Involvement of bystander effect in suppression of the cytokine production induced by heavy-ion broad beams

Muto, Yasuko; Funayama, Tomoo; Yokota, Yuichiro; Kobayashi, Yasuhiko

International Journal of Radiation Biology, 88(3), p.258 - 266, 2012/03

 Times Cited Count:11 Percentile:69.17(Biology)

Journal Articles

Applications of the microdosimetric function implemented in the macroscopic particle transport simulation code PHITS

Sato, Tatsuhiko; Watanabe, Ritsuko; Sihver, L.*; Niita, Koji*

International Journal of Radiation Biology, 88(1-2), p.143 - 150, 2012/01

 Times Cited Count:14 Percentile:76.37(Biology)

The microdosimetric function of PHITS has been applied to the biological dose estimation for charged-particle therapy and the risk estimation for astronauts. The former application was performed in combination with the microdosimetric kinetic model, while the latter was done with the radiation quality factor expressed as a function of lineal energy. Owing to the unique features of the microdosimetric function, the improved PHITS has a potential to establish more sophisticated systems for the radiological protection in space as well as the treatment planning of charged-particle therapy.

Journal Articles

Mutational effects of different LET radiations in ${it rpsL}$ transgenic ${it Arabidopsis}$

Yoshihara, Ryohei; Hase, Yoshihiro; Sato, Ryohei*; Takimoto, Koichi*; Narumi, Issei

International Journal of Radiation Biology, 86(2), p.125 - 131, 2010/02

 Times Cited Count:18 Percentile:79.59(Biology)

In an effort to assess the characteristics of mutation induced by different LET radiation in higher plants, the mutational effects of carbon-ion beams and $$gamma$$-rays were investigated in ${it Arabidopsis}$. The ${it rpsL}$ transgenic ${it Arabidopsis}$ (Arabidopsis/rpsL) mutation detection system was adopted. Dry seeds of Arabidopsis/rpsL were irradiated with $$gamma$$-rays and 208-MeV carbon ions (208-MeV $$^{12}$$C$$^{5}$$), and the mutation frequency and mutation spectrum were examined. Our result suggested that 208-MeV $$^{12}$$C$$^{5}$$ and $$gamma$$-rays induced different mutational effects in ${it Arabidopsis}$ dry seed.

Journal Articles

Studies of soft X-ray-induced Auger effect on the induction of DNA damage

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:65.48(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 ($$sim$$60 keV) induced lesions visualized by the enzymatic probes show much higher yields than those induced by low LET $$gamma$$-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.

Journal Articles

Induction of single strand breaks, and base lesions in plasmid DNA films induced by carbon, nitrogen, and oxygen KLL Auger process

Fujii, Kentaro; Yokoya, Akinari; Shikazono, Naoya

International Journal of Radiation Biology, 84(12), p.1104 - 1111, 2008/12

 Times Cited Count:5 Percentile:31.93(Biology)

To investigate the KLL Auger 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 560 eV, 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.

Journal Articles

Characterization of lesions induced in linear-formed plasmid DNA by valence ionization and Auger decay at carbon, nitrogen and oxygen

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 $$gamma$$-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 $$gamma$$-rays. Furthermore, piperidine-treated irradiated DNA was also analyzed by the same method above to quantify piperidine-labile base lesions.

Journal Articles

LET dependence of the yield of single-, double-strand breaks and base lesions in fully hydrated plasmid DNA films by $$^{4}$$He$$^{2+}$$ ion irradiation

Urushibara, Ayumi*; Shikazono, Naoya; O'Neill, P.*; Fujii, Kentaro; Wada, Seiichi*; Yokoya, Akinari

International Journal of Radiation Biology, 84(1), p.23 - 33, 2008/01

 Times Cited Count:33 Percentile:90.3(Biology)

To characterize the complexity of radiation damage to DNA, fully hydrated plasmid DNA was irradiated with $$^{4}$$He$$^{2+}$$ ions. From quantification of the conformational changes of the irradiated samples, the yields of single-(SSB) and double strand break (DSB) were obtained. Base lesions were visualized as additional strand breaks by treatment with base excision repair enzymes. The yield of prompt SSBs does not depend significantly on LET of the $$^{4}$$He$$^{2+}$$ ions, whereas the yield of prompt DSBs increases with increasing LET. The yields of isolated base lesions, revealed by enzymes as additional SSBs, decrease drastically with increasing LET. The sum of the yields of DSB and additional DSBs revealed by the enzymes increase with increasing LET of the $$^{4}$$He$$^{2+}$$ ions except at the highest LET investigated. These results indicate that the yields of clustered damage, revealed as DSB and non-DSB clustered damage sites, increase with increasing ionization density of radiation.

Journal Articles

Role of DNA-PKcs in the bystander effect after low- or high-LET irradiation

Kanasugi, Yuichi*; Hamada, Nobuyuki*; Wada, Seiichi*; Funayama, Tomoo; Sakashita, Tetsuya; Kakizaki, Takehiko; Kobayashi, Yasuhiko; Takakura, Kaoru*

International Journal of Radiation Biology, 83(2), p.73 - 80, 2007/02

 Times Cited Count:30 Percentile:89.28(Biology)

no abstracts in English

Journal Articles

Radiation tolerance in the tardigrade ${it Milnesium tardigradum}$

Horikawa, Daiki*; Sakashita, Tetsuya; Katagiri, Chihiro*; Watanabe, Masahiko*; Kikawada, Takahiro*; Nakahara, Yuichi*; Hamada, Nobuyuki*; Wada, Seiichi*; Funayama, Tomoo; Higashi, Seigo*; et al.

International Journal of Radiation Biology, 82(12), p.843 - 848, 2006/12

 Times Cited Count:110 Percentile:99.11(Biology)

no abstracts in English

34 (Records 1-20 displayed on this page)