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Journal Articles

The Impact of dose rate on responses of human lens epithelial cells to ionizing irradiation

Matsuya, Yusuke; Sato, Tatsuhiko; Yachi, Yoshie*; Date, Hiroyuki*; Hamada, Nobuyuki*

Scientific Reports (Internet), 14, p.12160_1 - 12160_14, 2024/05

Understand mechanisms of radiation cataracts that are of concern in the field of radiation protection and radiation therapy. However, biological effects in HLEC following protracted exposure have not yet fully been explored. Here, we investigated the temporal kinetics of DNA double-strand breaks (DSBs) and cell survival of HLEC after exposure to photon beams at various dose rates, compared to those of human lung fibroblasts (WI-38). In parallel, we quantified the recovery for DSB and cell survival using a biophysical model. The study revealed that HLEC cells have a lower repair rate than WI-38 cells. There is no significant impact of dose rate on cell survival in both cell lines in the dose-rate range of 0.033-1.82 Gy/min. On the other hand, the experimental residual DSBs showed inverse dose rate effects (IDREs) compared to the model prediction, highlighting the importance of the IDREs in evaluating radiation effects on the ocular lens.

Journal Articles

Regulatory implementation of the occupational equivalent dose limit for the lens of the eye and underlying relevant efforts in Japan

Yokoyama, Sumi*; Hamada, Nobuyuki*; Tsujimura, Norio; Kunugita, Naoki*; Nishida, Kazutaka*; Ezaki, Iwao*; Kato, Masahiro*; Okubo, Hideki*

International Journal of Radiation Biology, 99(4), p.604 - 619, 2023/04

 Times Cited Count:2 Percentile:32.94(Biology)

In April 2011, the International Commission on Radiological Protection recommended reducing the occupational equivalent dose limit for the lens. Such a new occupational lens dose limit has thus far been implemented in many countries, and there are extensive discussions toward its regulatory implementation in other countries. In Japan, discussions in the Japan Health Physics Society (JHPS) began in April 2013 and in Radiation Council in July 2017, and the new occupational lens dose limit was implemented into regulation in April 2021. To share our experience, we have published a series of papers summarizing situations in Japan: the first paper based on information available by early 2017, and the second paper by early 2019. This paper (our third paper of this series) aims to review updated information available by mid-2022, such as regarding regulatory implementation of the new occupational lens dose limit, recent discussions by relevant ministries based on the opinion from the council, establishment process of safety and health management systems, the JHPS guidelines on lens dose monitoring and radiation safety, voluntary countermeasures of the licensees, development of lens dose calibration method, and recent studies on exposure of the lens in nuclear workers and biological effect on the lens.

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, 114(1), p.153 - 162, 2022/09

 Times Cited Count:6 Percentile:79.29(Oncology)

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

Inflammatory signaling and DNA damage responses after local exposure to an insoluble radioactive microparticle

Matsuya, Yusuke; Hamada, Nobuyuki*; Yachi, Yoshie*; Satou, Yukihiko; Ishikawa, Masayori*; Date, Hiroyuki*; Sato, Tatsuhiko

Cancers (Internet), 14(4), p.1045_1 - 1045_15, 2022/02

 Times Cited Count:9 Percentile:85.70(Oncology)

An insoluble cesium-bearing microparticle (Cs-BMP) was discovered after the incident at the Fukushima nuclear power plant. Radiation risk by intake of internal exposure to radioactive cesium is conventionally estimated from organ dose, assuming that soluble cesium is uniformly distributed throughout human body. Meanwhile, such Cs-BMPs are assumed to adhere in the long term to normal tissue, leading to chronic non-uniform exposure. In this study, to clarify the normal tissue effects for Cs-BMP exposure, we investigated the relationship between the inflammatory responses and DNA damage induction. From experiments focusing on the inflammatory signaling pathways such as NF-$$kappa$$B p65 and COX-2, compared to the uniform exposure to $$gamma$$-rays, NF-$$kappa$$B p65 tended to be more activated in the cells proximal to the Cs-BMP, while both NF-$$kappa$$B p65 and COX-2 were significantly activated in the distal cells. Experiments with inhibitors for NF-$$kappa$$B p65 and COX-2 suggested involvement of such inflammatory responses both in the reduced radiosensitivity of the cells proximal to Cs-BMP and the enhanced radiosensitivity of the cells distal from Cs-BMP. These results suggested that radiation effects for Cs-BMP exposure can differ from that estimated based on conventional uniform exposure to normal tissues.

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:9 Percentile:62.50(Biology)

Journal Articles

A Biologically based mathematical model for spontaneous and ionizing radiation cataractogenesis

Sakashita, Tetsuya*; Sato, Tatsuhiko; Hamada, Nobuyuki*

PLOS ONE (Internet), 14(8), p.e0221579_1 - e0221579_20, 2019/08

 Times Cited Count:8 Percentile:46.27(Multidisciplinary Sciences)

Cataracts have long been known, but a biologically based mathematical model is still unavailable for cataratogenesis. We here report for the first time an in silico model for cataractogenesis. First, a simplified cell proliferation model was developed for human lens growth based on stem and progenitor cell proliferation as well as epithelial-fiber cell differentiation. Then, a model for spontaneous cataractogenesis was developed to reproduce the human data on a relationship between age and cataract incidence. Finally, a model for radiation cataractogenesis was developed that can reproduce the human data on a relationship between dose and cataract onset at various ages, which was further applied to estimate cataract incidence following chronic lifetime exposure.

Journal Articles

DNA damage induction during localized chronic exposure to an insoluble radioactive microparticle

Matsuya, Yusuke; Satou, Yukihiko; Hamada, Nobuyuki*; Date, Hiroyuki*; Ishikawa, Masayori*; Sato, Tatsuhiko

Scientific Reports (Internet), 9(1), p.10365_1 - 10365_9, 2019/07

 Times Cited Count:12 Percentile:61.32(Multidisciplinary Sciences)

Insoluble radioactive microparticles (so called Cs-bearing particles) have been assumed to adhere in the long term to trachea after aspirated into respiratory system, leading to heterogeneous dose distribution within healthy tissue around the particles. The biological effects posed by such a particle remain unclear. Here, we show cumulative DNA damage in cultured cells proximal and distal to the particle under localized chronic exposure in comparison with uniform exposure. We placed the particle-contained microcapillary onto a glass-base dish containing normal human lung cells in vitro, and observed a significant change in nuclear $$gamma$$-H2AX foci after 24 h or 48 h exposure to the particle. The dose calculation by a Monte Carlo simulation and the comparison with nuclear foci under uniform exposure suggested that the localized exposure to a Cs-bearing particle leads to not only signal-induced DNA damage to distal cells but also the reduction of DNA damage induction yield to proximal cells (protective effects). Considering the small organ dose, the conventional radiation risk assessment is adequate. This study is the first to quantify the spatial distribution of cumulative DNA lesions under heterogeneous exposure by insoluble Cs-bearing particles.

Journal Articles

Depth distributions of RBE-weighted dose and photon-isoeffective dose for boron neutron capture therapy

Sato, Tatsuhiko; Masunaga, Shinichiro*; Kumada, Hiroaki*; Hamada, Nobuyuki*

Radiation Protection Dosimetry, 183(1-2), p.247 - 250, 2019/05

 Times Cited Count:7 Percentile:60.64(Environmental Sciences)

As an application of Particle and Heavy Ion Transport code System PHITS, We have developed the stochastic microdosimetric kinetic (SMK) model for estimating the therapeutic effects of various kinds of radiation therapy. In this study, we improved the SMK model for estimating the therapeutic effect of boron neutron capture therapy, BNCT. The improved SMK model can consider not only the intra- and intercellular heterogeneity of B-10 distribution but also the dose rate effect. The accuracy of the model was well verified by comparisons made between calculated and measured surviving fractions of tumor cells, which we previously determined in vivo in mice with B-10 compounds exposed to reactor neutron beam. Details of the improved SMK model together with the verification results will be presented at the meeting.

Journal Articles

Microdosimetric modeling of biological effectiveness for boron neutron capture therapy considering intra- and intercellular heterogeneity in $$^{10}$$B distribution

Sato, Tatsuhiko; Masunaga, Shinichiro*; Kumada, Hiroaki*; Hamada, Nobuyuki*

Scientific Reports (Internet), 8(1), p.988_1 - 988_14, 2018/01

 Times Cited Count:48 Percentile:93.42(Multidisciplinary Sciences)

We here propose a new model for estimating the biological effectiveness for boron neutron capture therapy (BNCT) considering intra- and intercellular heterogeneity in $$^{10}$$B distribution. The new model was developed from our previously established stochastic microdosimetric kinetic model that determines the surviving fraction of cells irradiated with any radiations, their synergetic effect being taken into account. The model can predict the biological effectiveness of newly developed $$^{10}$$B compounds based on their intra- and intercellular distributions, and thus, it can play important roles not only in treatment planning but also in drug discovery research for future BNCT.

Journal Articles

Current situations and discussions in Japan in relation to the new occupational equivalent dose limit for the lens of the eye

Yokoyama, Sumi*; Hamada, Nobuyuki*; Hayashida, Toshiyuki*; Tsujimura, Norio; Tatsuzaki, Hideo*; Kurosawa, Tadahiro*; Nabatame, Kuniaki*; Oguchi, Hiroyuki*; Ono, Kazuko*; Kawaura, Chiyo*; et al.

Journal of Radiological Protection, 37(3), p.659 - 683, 2017/09

 Times Cited Count:15 Percentile:81.45(Environmental Sciences)

Since the International Commission on Radiological Protection recommended reducing the occupational equivalent dose limit for the lens of the eye in 2011, there have been extensive discussions in various countries. This paper reviews the current situations in radiation protection of the ocular lens and the discussions on the potential impact of the new lens dose limit in Japan. Topics include historical changes to the lens dose limit, the current situations in occupational lens exposures (e.g., in medical workers, nuclear workers, and Fukushima nuclear power plant workers) and measurements, and the current status of biological studies and epidemiological studies on radiation cataracts. Our focus is on the situations in Japan, but we believe such information sharing will be useful in many other countries.

Journal Articles

Report on the Workshop "Radiation Research Based on Computer Simulation" held at the 59th Annual Meeting of the Japanese Radiation Research Society

Sato, Tatsuhiko; Hamada, Nobuyuki*

Hoshasen Seibutsu Kenkyu, 51(4), p.397 - 401, 2016/12

A workshop entitled "Radiation Research Based on Computer Simulation" was held at the 59th annual meeting of the Japanese Radiation Research Society. Approximately 50 participants attended the workshop, and six speakers gave a talk about their computational radiation biology studies. The title of the presentations are "Research on DNA damage and track structure simulation", "Study of cellular response based on stochastic model for simulating irradiated and non-irradiated cells", "Effectiveness of mathematical model for low-dose radiation effect", "Research on particle therapy based on cell surviving fraction model", "Development of model for natural induction of cataract", and "Mathematical model for carcinogenesis considering the differences of temporal and spatial doses". In the workshop, possible future collaborations were intensively discussed. This report briefly summarizes the outline of the workshop.

Journal Articles

Cataractogenesis following high-LET radiation exposure

Hamada, Nobuyuki*; Sato, Tatsuhiko

Mutation Research; Reviews in Mutation Research, 770(Part B), p.262 - 291, 2016/10

 Times Cited Count:32 Percentile:51.44(Biotechnology & Applied Microbiology)

From the radiation protection viewpoint, the ocular lens is among the most radiosensitive tissues in the body, and cataract is classified as tissue reactions with a threshold below which no effect would occur. After 2011, the International Commission on Radiological Protection (ICRP) has recommended an equivalent dose limit for the lens to 20 mSv/year. Although such reduction of the threshold was based on findings from low-LET radiation, the dose limit was recommended in Sv. This review is thus designed to provide an update on the current knowledge as to high-LET radiation cataractogenesis. To this end, changes in ICRP recommendations on lenticular radiation protection, epidemiological and biological findings on high-LET cataractogenesis are reviewed, and future research needs are then discussed.

Journal Articles

Summary of ICRP Symposium on Radiological Protection Dosimetry

Endo, Akira; Hamada, Nobuyuki*

Isotope News, (745), p.42 - 43, 2016/06

ICRP Symposium on Radiological Protection Dosimetry was held in Hongo campus, the University of Tokyo on February 18, 2016. Committee 2 of the International Commission on Radiological Protection (ICRP) is engaged in the development of dose coefficients for the assessment of internal and external radiation exposures; development of reference biokinetic and dosimetric models, and reference data for workers and members of the public. The symposium aimed at reviewing the current work of ICRP and discussing research needed for the ICRP System of radiological protection dosimetry. This article reviews the presentations and discussion in the symposium.

Journal Articles

Addendum report of the JHPS expert committee on radiation protection of the lens of the eye, 2; When and how should the dosimetry of beta $$H_{rm p}$$(3) be made?

Akahane, Keiichi*; Iimoto, Takeshi*; Ichiji, Takeshi*; Iwai, Satoshi*; Oguchi, Hiroyuki*; Ono, Kazuko*; Kawaura, Chiyo*; Kurosawa, Tadahiro*; Tatsuzaki, Hideo*; Tsujimura, Norio; et al.

Hoken Butsuri, 50(4), p.257 - 261, 2015/12

In a mixed field of photon and beta radiations, the same dose assigned to skin is normally assigned to the dose to the lens of the eye as a conservative estimate of H$$_{p}$$(3). In exceptional cases that a very high beta dose might be imparted of the same order with the dose limit, however, the conservatively biased dose must be too limiting, and thereby an accurate estimate of beta $$H_{rm p}$$(3) is desirable. This article presents a practical proposal of when and how the dosimetry of beta $$H_{rm p}$$(3) should be made.

Journal Articles

Responses of the salt chemotaxis learning in ${it C. elegans}$ mutants to microbeam irradiation

Sakashita, Tetsuya; Suzuki, Michiyo; Hattori, Yuya; Ikeda, Hiroko; Muto, Yasuko*; Yokota, Yuichiro; Funayama, Tomoo; Hamada, Nobuyuki*; Shirai, Kana*; Kobayashi, Yasuhiko

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 74, 2015/03

An increasing body of data indicates that ionizing radiation affects the nervous system and alters its function. Recently, we reported that chemotaxis of ${it C. elegans}$ during the salt chemotaxis learning (SCL), that is conditioned taste aversion to NaCl, was modulated by carbon ion irradiation, i.e. accelerated decrease in chemotaxis to NaCl during the SCL. However, we had no direct evidence for the interaction of ionizing radiation with the central neuronal tissue (nerve ring) in ${it C. elegans}$. Microbeam irradiation is useful to analyze direct radiation effects at a cellular or tissue level. Thus, we applied the microbeam irradiation of the ${it C. elegans}$ nerve ring and examined the effect on the SCL.

Journal Articles

Model assembly for estimating cell surviving fraction for both targeted and nontargeted effects based on microdosimetric probability densities

Sato, Tatsuhiko; Hamada, Nobuyuki*

PLOS ONE (Internet), 9(11), p.e114056_1 - e114056_20, 2014/11

 Times Cited Count:11 Percentile:42.57(Multidisciplinary Sciences)

We here propose a new model assembly for estimating the surviving fraction of cells irradiated with various types of ionizing radiation, considering both targeted and nontargeted effects in the same framework. The probability densities of specific energies in cell nucleus and domain calculated by PHITS were employed as the physical index for characterizing the radiation fields. In the model assembly, our previously established double stochastic microdosimetric kinetic (DSMK) model was used to express the targeted effect, whereas a newly developed model was used to express the nontargeted effect. The radioresistance caused by overexpression of anti-apoptotic protein Bcl-2 known to frequently occur in human cancer was also considered by introducing the concept of the adaptive response in the DSMK model. The accuracy of the model assembly was examined by comparing the computationally and experimentally determined surviving fraction of Bcl-2 and Neo cells irradiated with microbeam or broadbeam of energetic heavy ions, as well as the WI-38 normal human fibroblasts irradiated with X-ray microbeam. The model assembly reproduced very well the experimentally determined surviving fraction over a wide range of dose and linear energy transfer (LET) values. Our newly established model assembly will be worth being incorporated into treatment planning systems for heavy-ion therapy, brachytherapy, and boron neutron capture therapy, given critical roles of the frequent Bcl-2 overexpression and the nontargeted effect in estimating therapeutic outcomes and harmful effects of such advanced therapeutic modalities.

Journal Articles

Interim report of the JHPS expert committee on radiation protection of the lens of the eye, 2; The Dosimetry method for the lens of the eye of workers in Japan

Akahane, Keiichi*; Iimoto, Takeshi*; Ichiji, Takeshi*; Iwai, Satoshi*; Oguchi, Hiroyuki*; Ono, Kazuko*; Kawaura, Chiyo*; Tatsuzaki, Hideo*; Tsujimura, Norio; Hamada, Nobuyuki*; et al.

Hoken Butsuri, 49(3), p.153 - 156, 2014/09

A brief review is given of the history and methodology of external dosimetry for the lens of the eye. Under the 1989 revision to domestic radiological protection regulations, the concept on the effective dose equivalent and the dose limit to the lens of the eye (150 mSv/y) both introduced in ICRP 1977 recommendations has changed nationwide the external monitoring methodology in non-uniform exposure situations to the trunk of a radiological worker. In such situations, often created by the presence of a protective apron, the worker is required to use at least two personal dosemeters, one worn on the trunk under the apron and the other, typically, at the collar over the apron. The latter dosemeter serves the dual purpose of providing the dose profile across the trunk for improved effective dose equivalent assessment and of estimating the dose to lens of the eye. The greater or appropriate value between $$H_{rm p}$$(10) and $$H_{rm p}$$(0.07), given by the dosemeter, is generally used as a surrogate of $$H_{rm p}$$(3).

Journal Articles

Novel findings obtained with the colony formation assay of normal human cells

Hamada, Nobuyuki*; Sakashita, Tetsuya; Hara, Takamitsu*; Fujimichi, Yuki*

Hoshasen Seibutsu Kenkyu, 49(3), p.318 - 331, 2014/09

Over the past half century, a colony formation assay has been most commonly used to evaluate cellular radiosensitivity. Our colony formation assay of primary normal human diploid fibroblasts and the analysis of the size and cell numbers in abortive colonies comprising $$<$$ 50 cells and clonogenic colonies comprising $$geq$$ 50 cells led to observations that can potentially answer a fundamental question of what is actually being evaluated in the colony formation assay, and a new phenomenon was also unveiled with the colony formation assay whereby the higher the dose the larger the size of colonies arising from irradiated primary normal human diploid ocular lens epithelial cells. This paper shall review these findings.

Journal Articles

Microdosimetric analysis confirms similar biological effectiveness of external exposure to $$gamma$$-rays and internal exposure to $$^{137}$$Cs, $$^{134}$$Cs, and $$^{131}$$I

Sato, Tatsuhiko; Manabe, Kentaro; Hamada, Nobuyuki*

PLOS ONE (Internet), 9(6), p.e99831_1 - e99831_10, 2014/06

 Times Cited Count:9 Percentile:36.56(Multidisciplinary Sciences)

The RBEs of the internal exposure to $$^{137}$$Cs, $$^{134}$$Cs and $$^{131}I$$ were evaluated on the basis of the microdosimetric analysis.

Journal Articles

A Branching process model for the analysis of abortive colony size distributions in carbon ion-irradiated normal human fibroblasts

Sakashita, Tetsuya; Hamada, Nobuyuki*; Kawaguchi, Isao*; Hara, Takamitsu*; Kobayashi, Yasuhiko; Saito, Kimiaki

Journal of Radiation Research, 55(3), p.423 - 431, 2014/02

 Times Cited Count:3 Percentile:17.44(Biology)

Our previous analysis with a branching process model showed that the relative cell death (RCD) in human fibroblasts can persist over 16 generations following irradiation with low linear energy transfer (LET) $$gamma$$-rays. Here we further set out to evaluate the RCD persistency in abortive colonies arising from normal human fibroblasts exposed to high-LET carbon ions (18.3 MeV/u, 108 keV/$$mu$$m). We found that the abortive colony size distribution determined by biological experiments follows the linear relationship on the log-log plot, and that the Monte Carlo simulation using the RCD probability estimated from such linear relationship well simulates the experimentally determined surviving fraction and the relative biological effectiveness (RBE). We identified the short-term phase and long-term phase for the persistent RCD, as was the case for $$gamma$$-irradiation.

303 (Records 1-20 displayed on this page)