Inverse dose protraction effects of low-LET radiation; Evidence and significance

Hamada, Nobuyuki*; Matsuya, Yusuke; Zablotska, L. B.*; Little, M. P.*

Mutation Research; Reviews in Mutation Research, 795, p.108531_1 - 108531_38, 2025/01

https://doi.org/10.1016/j.mrrev.2025.108531

Biological effects of ionizing radiation vary not merely with total dose but also with temporal dose distribution. While sparing dose protraction effects where dose protraction reduces effects of radiation have widely been accepted and generally assumed in radiation protection, inverse dose protraction effects (IDPEs) where dose protraction enhances radiation effects have not been well recognized, nor comprehensively reviewed. Here, we review the current knowledge on IDPEs of low LET radiation. Since 1952, 136 biology, epidemiology or clinical papers have heretofore reported IDPEs following low-LET irradiation (i.e., photons, -rays, electrons, protons or helium ions) using cell-free macromolecules (DNA, proteins, or lipids), cultured mammalian cells, insects, animals, and human. In contrast to a growing body of phenomenological evidence for manifestations of IDPEs, there is limited knowledge on mechanistic underpinnings. This review will contribute to ongoing research into the mechanism and to the discussion of the implications of the scientific evidence for radiation protection.

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

https://doi.org/10.1038/s41598-024-62679-8

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.

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

https://doi.org/10.1016/j.ijrobp.2022.05.010

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.

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

https://doi.org/10.1080/09553002.2019.1605464

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

https://doi.org/10.1038/s41598-019-46874-6

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 -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.

Microdosimetric modeling of biological effectiveness for boron neutron capture therapy considering intra- and intercellular heterogeneity in B distribution

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

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

https://doi.org/10.1038/s41598-017-18871-0

We here propose a new model for estimating the biological effectiveness for boron neutron capture therapy (BNCT) considering intra- and intercellular heterogeneity in 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 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.

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.

Summary of ICRP Symposium on Radiological Protection Dosimetry

Endo, Akira; Hamada, Nobuyuki*

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

http://www.jrias.or.jp/books/pdf/201606_MONITORING_ENDO_HAMADA.pdf

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.

Responses of the salt chemotaxis learning in 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

https://doi.org/10.11484/jaea-review-2014-050

An increasing body of data indicates that ionizing radiation affects the nervous system and alters its function. Recently, we reported that chemotaxis of 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 . Microbeam irradiation is useful to analyze direct radiation effects at a cellular or tissue level. Thus, we applied the microbeam irradiation of the nerve ring and examined the effect on the SCL.

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

https://doi.org/10.5453/jhps.49.153

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 (10) and (0.07), given by the dosemeter, is generally used as a surrogate of (3).