福永 久典 (フクナガ ヒサノリ)
| 保健科学研究院 保健科学部門 医用生体理工学分野 | 准教授 |
| 高等教育推進機構 | 准教授 |
| One Healthリサーチセンター | 准教授 |
Last Updated :2026/04/20
■研究者基本情報
プロフィール情報
2011年の東日本大震災および福島第一原子力発電所事故後、福島県・公立相馬総合病院で被災地医療に携わったことから、放射線被ばくによる健康リスクを科学的根拠に基づいて理解し、社会へ還元する医学研究の重要性を痛感しました。そして、この経験を原点として、分子レベルから個体レベルまでに至る放射線影響の解明と、被ばくに伴う健康リスクの予測と対策に取り組んできました。
現在、量子ビーム技術や遺伝子改変マウスなどを用いて、空間的に分割された放射線照射後の組織応答の解明を進めるとともに、放射線被ばく後のミトコンドリアゲノム損傷応答や代謝変容に着目した次世代影響研究を行っています。これらの成果によって、放射線健康リスクの理解をより深化させるだけでなく、より安全で効率的な放射線制御技術・イノベーションの創出も目指しています。
Researchmap個人ページ
■経歴
■研究活動情報
受賞
- 2026年04月, 北海道大学大学院保健科学研究院, 保健科学研究院長賞
福永 久典, 北海道大学大学院保健科学研究院の顕彰に関する内規(抜粋)
第2条 大学院保健科学研究院長(以下「研究院長」という。)は,研究等に関し,顕著な業績等のあった教員(国立大学法人北海道大学特任教員就業規則(平成18年海大達第35号)第3条第2号に該当する特任教員を含む。)を顕彰することができる。
2 顕彰の種類及び対象者は次の各号に掲げるとおりとする。
(1) 保健科学研究院長賞
顕著な業績により本研究院の名誉を著しく高めた教員
(2) 保健科学研究院優秀論文賞
特に優れた質の高い論文を発表した教員(第1著者又は連絡著者,もしくは両者)。, その他の賞, 日本国 - 2026年03月, National Council on Radiation Protection and Measurements, John D. Boice, Jr. Young Investigator Award
Hisanori Fukunaga, 国内外の国際的学術賞, アメリカ合衆国 - 2025年04月, 北海道大学大学院保健科学研究院, 保健科学研究院優秀論文賞
福永 久典, 北海道大学大学院保健科学研究院の顕彰に関する内規(抜粋)
第2条 大学院保健科学研究院長(以下「研究院長」という。)は,研究等に関し,顕著な業績等のあった教員(国立大学法人北海道大学特任教員就業規則(平成18年海大達第35号)第3条第2号に該当する特任教員を含む。)を顕彰することができる。
2 顕彰の種類及び対象者は次の各号に掲げるとおりとする。
(1) 保健科学研究院長賞
顕著な業績により本研究院の名誉を著しく高めた教員
(2) 保健科学研究院優秀論文賞
特に優れた質の高い論文を発表した教員(第1著者又は連絡著者,もしくは両者)。, その他の賞, 日本国 - 2023年11月, International Commission on Radiological Protection (ICRP), ICRP Cousins Award Finalist
"Rethinking tissue reactions to radiation: The tissue-sparing effect as a threshold for radiation-induced male infertility"
Hisanori Fukunaga, 国内外の国際的学術賞, カナダ - 2022年11月, Asian Association for Radiation Research (AARR), AARR Young Scientist Award
Hisanori Fukunaga, 国際学会・会議・シンポジウム等の賞, インド - 2022年10月, 北海道大学, 第8回北海道大学部局横断シンポジウム研究奨励賞 銀賞
福永 久典, 国内学会・会議・シンポジウム等の賞, 日本国 - 2022年09月, 公益財団法人中山人間科学振興財団, 中山賞奨励賞
「マイクロビームによる精密な空間制御と精子形成能の温存―マイクロビーム放射線治療の開発」
福永 久典, 出版社・新聞社・財団等の賞, 日本国 - 2021年11月, 国立研究開発法人科学技術振興機構, 創発研究者
福永 久典, その他の賞, 日本国 - 2021年10月, Radiation Research Society, Radiation Research Editors' Award
Hisanori Fukunaga, 学会誌・学術雑誌による顕彰, アメリカ合衆国 - 2021年06月, 一般社団法人日本保健物理学会, 日本保健物理学会 奨励賞
「マイクロビームと組織培養を用いた放射線組織生物学―保健物理学と放射線生物学の接点として―」
福永 久典, 国内学会・会議・シンポジウム等の賞, 日本国 - 2020年07月, 文部科学省, 令和2年度卓越研究員候補者
福永 久典, その他の賞, 日本国 - 2020年04月, 公益財団法人放射線影響協会, 放射線影響研究奨励賞
「シンクロトロン放射光X線マイクロビームと精巣器官培養法を用いた不均一な放射線被ばく後の精子形成能の検討」
福永 久典, 出版社・新聞社・財団等の賞, 日本国 - 2019年07月, 独創性を拓く先端技術大賞 フジテレビジョン賞
「不均一な放射線被ばく後の精子形成能の検討 ~原子力災害後の環境放射線被ばくリスクの解明を目指して~」
福永 久典, 主催:フジサンケイ ビジネスアイ
後援:文部科学省、経済産業省、フジテレビジョン、産経新聞社、ニッポン放送, 出版社・新聞社・財団等の賞, 日本国 - 2018年10月, CONCERT Travel Award, European Joint Programme for the Integration of Radiation Protection Research (CONCERT) (EU)
Hisanori Fukunaga, 国際学会・会議・シンポジウム等の賞, ドイツ連邦共和国 - 2017年10月, Scholar-In-Training Travel Award, Radiation Research Society (USA)
Hisanori Fukunaga, 国際学会・会議・シンポジウム等の賞, アメリカ合衆国 - 2017年07月, 第148回東北大学加齢医学研究所集談会 優秀発表賞
福永 久典, 第31回加齢研研究員会主催発表コンテスト, 国内学会・会議・シンポジウム等の賞, 日本国 - 2016年10月, International Studentship, Queen's University Belfast (UK)
Hisanori Fukunaga, その他の賞, グレートブリテン・北アイルランド連合王国(英国) - 2016年02月, 平成27年度福島県地域医療症例検討会 準グランプリ
福永 久典, 国内学会・会議・シンポジウム等の賞, 日本国 - 2015年12月, 公立相馬総合病院 優秀職員表彰
福永 久典, その他の賞, 日本国 - 2013年06月, GRE Summer School 2013 Vacation Studentship, Centre for Gene Regulation and Expression, University of Dundee (UK)
Hisanori Fukunaga, その他の賞, グレートブリテン・北アイルランド連合王国(英国) - 2012年09月, 第49回アイソトープ・放射線研究発表会 若手優秀発表賞
福永 久典, 国内学会・会議・シンポジウム等の賞, 日本国 - 2011年03月, 横浜市立大学長奨励賞
福永 久典, その他の賞, 日本国 - 2010年10月, 横浜市立大学医学部長賞(金賞)
福永 久典, その他の賞, 日本国
論文
- Mitochondrial DNA alterations in mothers and offspring following in utero exposure to ionizing radiation.
Ryosuke Seino, Haruka Kubo, Atsuko Ikeda, Hisanori Fukunaga
Free Radical Biology and Medicine, 250, 168, 173, Elsevier BV, 2026年03月28日, [査読有り], [招待有り], [最終著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Ionizing radiation can perturb mitochondrial homeostasis and genomic stability, yet its developmental consequences remain insufficiently understood. We investigated how in utero X-ray exposure may affect mitochondrial DNA (mtDNA) regulation and developmental parameters in a mouse model. Pregnant C57BL/6N mice were exposed to 0 (sham-irradiated), 0.05, 0.2, 0.5 and 2 Gy X-rays at gestational day 8, corresponding to the onset of organogenesis. In maternal peripheral blood, mtDNA copy number (mtDNAcn) increased at 2 Gy, while the intact mtDNA ratio, defined as the degree of mtDNA homoplasy estimated by long-fragment PCR, decreased at ≥ 0.5 Gy. Pregnancy resulted in live offspring at GD8 X-ray doses of 0.5 Gy or lower. Offspring sex ratios and body weights did not differ between control and irradiated groups. Notably, offspring examined at two weeks of age exhibited significantly elevated mtDNAcn at ≥ 0.2 Gy, whereas intact mtDNA ratios were unchanged. These results demonstrate that in utero X-ray exposure is associated with dose-dependent alterations in mtDNA regulation in both mothers and their offspring, with distinct sensitivities observed between maternal and offspring responses. These findings highlight mitochondrial responses to radiation exposure during early development and suggest that prenatal irradiation may influence mtDNA regulation, with potential implications for mitochondrial function later in life. - Radiation‑induced impacts on female fertility and fecundity: perspectives from the viewpoint of radiation protection.
Hisanori Fukunaga, Nobuyuki Hamada
International Journal of Radiation Biology, 102, 3, 216, 220, Informa UK Limited, 2026年03月, [査読有り], [筆頭著者, 責任著者], [国際誌]
日本語, 研究論文(学術雑誌), Purpose: This mini-review aims to synthesize current knowledge regarding radiation-induced effects on female fertility and reproductive capacity, and to identify knowledge gaps relevant to radiation protection.
Methods: We critically examined evidence from developmental biology, animal models, clinical studies, and epidemiological investigations. Key topics include germ cell and follicle biology, radiation dose thresholds, therapeutic exposures, and environmental and occupational contexts.
Results: Female germ cells are highly radiosensitive, with animal models indicating a mean lethal dose as low as 0.05-0.15 Gy in primordial oocytes. In humans, pelvic irradiation increases risks of acute ovarian failure, premature ovarian insufficiency, and infertility, depending on dose and age at exposure. Cranial irradiation further impairs fertility through damage to the hypothalamic-pituitary axis. In contrast, evidence from occupational and environmental exposures is scarce, with most studies addressing miscarriage or perinatal outcomes rather than infertility itself.
Conclusions: While advances in oncofertility research have clarified therapeutic risks, systematic data on environmental and occupational exposures are lacking. Strengthened prospective studies and integration of fertility-specific biomarkers are urgently needed to inform comprehensive radiation protection strategies.
Keywords: Fecundity; fertility; ionizing radiation; ovarian reserve; radiation protection. - Intergenerational and organ-specific alterations in mitochondrial DNA copy number following preconception irradiation.
Ryosuke Seino, Hisanori Fukunaga
Redox Biology, 90, 104054, Elsevier BV, 2026年02月04日, [査読有り], [最終著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Ionizing radiation, a potent inducer of redox stress, perturbs both nuclear and mitochondrial genomes, yet how such stress shapes mitochondrial inheritance across generations remains unclear. In this study, we examined intergenerational and organ-specific mitochondrial responses to parental X-ray irradiation in mice. Eight-week-old male and female C57BL/6N mice were exposed to 2 Gy of single whole-body X-ray irradiation before mating, generating paternal-, maternal-, and dual-irradiated lineages. In the parents, peripheral blood-derived mitochondrial DNA copy number (mtDNAcn) transiently increased one day after exposure, consistent with a rapid mitochondrial response to redox stress. In newborn offspring, mtDNAcn displayed clear organ- and parent-of-origin specificity: brain mtDNAcn decreased in paternal- and dual-irradiation lineages, heart mtDNAcn remained unchanged, and liver mtDNAcn showed the most pronounced depletion across all irradiated lineages. No significant inter-organ correlations in mtDNAcn were observed. All irradiated lineages exhibited increased body weight and increased liver weight at birth, with a significant positive association between these traits. Liver weight was negatively associated with hepatic mtDNAcn. Multiple regression analysis further showed that maternal pre-exposure mtDNAcn and offspring hepatic mtDNAcn independently predicted neonatal liver weight. Taken together, these findings demonstrate that preconception irradiation induces acute mitochondrial responses in parents and is associated with intergenerational, organ-specific mtDNAcn dysregulation that manifests as offspring birth outcomes. Parental irradiation perturbs organ-specific mitochondrial genome regulation and predisposes the next generation to altered growth-related traits., 35821660 - Longitudinal Analysis of Male Fertility Using an Acr-Luc Knock-In Mouse Model: A Preclinical Platform for Reproductive Toxicity Testing.
Hisanori Fukunaga, Ryosuke Seino, Yusuke Matsuya, Hiroyuki Takashima, Masayori Ishikawa, Yasuhito Onodera, Hiroki Shirato, Haruhiko Miyata, Kevin M. Prise
MedComm, 7, 1, e70568, Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd., 2026年01月04日, [査読有り], [筆頭著者, 責任著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌), Reproductive toxicity testing is essential for evaluating whether xenobiotics, including pharmaceuticals, environmental chemicals, or ionizing radiation, adversely affect reproductive function. However, conventional assessments rely on mating outcomes or histopathology, which are labor‐intensive, variable, and require large numbers of animals. Acrosin, a serine protease encoded by the Acr gene and localized in the acrosome of spermatozoa, plays a critical role in sperm penetration of the zona pellucida. To exploit this germ cell‐specific expression, we generated a genetically engineered mouse model in which the Luciferase ( Luc ) reporter gene is driven by the Acr promoter. This Acr‐Luc knock‐in (KI) model enables longitudinal and quantitative imaging of spermatogenesis using bioluminescence. We demonstrate that this platform captures radiation‐induced impairments in male fertility in real time, eliminating the need for terminal analyses. By allowing repeated evaluation within the same individuals, our approach reduces interindividual variability and enables a substantial reduction in animal use, aligning with the “Reduction” principle of the 3Rs. Moreover, it reveals both the onset and recovery phases of spermatogenic disruption with high temporal resolution. The Acr‐Luc KI model provides a reliable preclinical platform for reproductive toxicity testing and offers broad utility for studies in reproductive biology, toxicology, and oncofertility research., 35821660 - Rethinking tissue reactions to radiation exposure: The tissue-sparing effect as a threshold for radiation- induced male infertility.
Hisanori Fukunaga, Kevin M. Prise
Annals of the ICRP, in press, International Commission on Radiological Protection, 2026年, [査読有り], [招待有り], [筆頭著者, 責任著者], [国際共著], [国際誌]
英語, 研究論文(国際会議プロシーディングス), The principle of microbeam radiotherapy (MRT) is the delivery of a single high-dose fraction to a large treatment area divided into several smaller fields, to reduce the treatment’s overall toxicity. Since the fundamental concept of MRT was first established, a notable tissue-sparing effect (TSE) has been confirmed in a large variety of species and tissue types, although the underlying biological mechanism in this process remains unclear. By coupling high-precision MRT with an ex-vivo mouse spermatogenesis model, we demonstrated the significant testicular TSE for maintaining spermatogenesis following MRT. To our knowledge, this was the first TSE identified in reproductive tissue. Our high precision microbeam analysis also revealed that an efficient TSE for spermatogenesis relies on the size of the non-irradiated germ stem cell pool in the irradiated testicular tissues, suggesting the involvement of stem cell migration/competition. These findings of testicular TSE indicate that radiation infertility is not dose-dependent, but instead depends on micro-dosimetric conditions, and that the limit of the TSE is a potential threshold for radiation-induced male infertility. - Radiation-induced changes in peripheral blood-derived mitochondrial DNA copy number and heteroplasmy in mice: Potential biomarkers of radiation exposure.
Ryosuke Seino, Yuka Takahashi, Hisanori Fukunaga
Biomedical Research, 46, 6, 257, 261, Biomedical Research Press, 2025年12月01日, [査読有り], [最終著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Radiological and nuclear accidents require reliable biomarkers for rapid detection of radiation exposure and dose estimation. While conventional biodosimetry has focused on nuclear DNA damage in lymphocytes, mitochondrial DNA (mtDNA) may provide an additional index because of its high copy number and limited repair capacity. Previous studies using Epstein–Barr virus-transformed lymphocytes and HeLa-FUCCI cells demonstrated radiation-induced changes in mtDNA copy number (mtDNAcn), suggesting compensatory replication as a characteristic response, but in vivo evidence has been limited. In this study, we analyzed peripheral blood from C57BL/6N male mice (8 weeks old) exposed to 0, 0.05, 0.2, 0.5, or 2 Gy of X-rays. MtDNAcn and intact copy ratio, defined as the proportion of undamaged copies, were quantified at 1 day and 1 week post-irradiation. We found that mtDNAcn was significantly increased only in the 2 Gy group at both 1 day and 1 week, whereas the intact copy ratio was significantly decreased in the 0.5 Gy and 2 Gy groups at 1 day but returned to baseline by 1 week. These findings indicate that peripheral blood-derived mtDNA indices are promising biomarkers for radiation biodosimetry, and that intact copy ratio may be particularly useful for detecting low-dose exposure. - Cord blood mitochondrial DNA copy number and physical growth in infancy and toddlerhood: A birth cohort analysis.
Hisanori Fukunaga, Takeshi Yamaguchi, Hiroyoshi Iwata, Atsuko Ikeda
Children, 12, 10, 1369, 2025年10月10日, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Background/Objectives: Cord blood mitochondrial DNA copy number (mtDNAcn) has been proposed as a biomarker reflecting environmental influences during fetal life, with reported associations with perinatal outcomes such as birth weight and length. Within the framework of the Developmental Origins of Health and Disease (DOHaD) theory, this study aimed to investigate whether cord blood mtDNAcn is related to postnatal physical growth in early childhood. Methods: We analyzed data from 150 newborns (68 females and 82 males) enrolled in the Tohoku Medical Megabank Birth and Three-Generation Cohort Study in Japan. Cord blood mtDNAcn was quantified using real-time PCR, and standard deviation scores for weight and height were assessed at 1, 2–3, 4–6, 18–24, and 36–48 months of age. Correlation analyses were conducted separately by sex. Results: Cord blood mtDNAcn showed no significant associations with body weight or height at any of the postnatal time points up to 48 months of age. Growth trajectories of infants with higher or lower mtDNAcn values at birth tended to converge toward the population mean during infancy and toddlerhood. Conclusions: Although no significant relationships were observed, this exploratory, hypothesis-generating study provides a foundation for future investigations. Larger cohorts with extended follow-up are needed to clarify the potential significance of cord blood mtDNAcn in early-life research on child growth and health., 32502774 - A Precise Re-Irradiation Supporting Tool Initiative (PRISTIN) for Prescribing Absorbed Dose and Number of fractions in Re-Irradiation.
Mayu Hagiwara, Ryusuke Suzuki, Seishin Takao, Rumiko Kinoshita, Shizusa Yamazaki, Keiji Nakazato, Hideki Kojima, Takayuki Hashimoto, Keiji Kobashi, Yasuhiro Onodera, Hisanori Fukunaga, Hidefumi Aoyama, Michael F Gensheimer, Masahiro Mizuta, Hiroki Shirato
Advances in Radiation Oncology, 10, 12, 101904, Elsevier BV, 2025年09月15日, [査読有り], [国際共著], [国際誌]
英語, 研究論文(学術雑誌), Purpose
This study aims to develop a supporting tool to calculate the most appropriate prescribing absorbed dose and number of fractions for precise reirradiation.
Methods and Materials
After deformable image registration of the initial computed tomography to the computed tomography at reirradiation, an initial biological effective dose (BED) taking into account the recovery from the initial irradiation is calculated voxel-by-voxel for each organ at risk (OAR). Using a commercial radiation therapy planning system, the clinical target volume for reirradiation (CTV2) is made. Keeping the BEDtumor’s α/β to CTV2, cumulative BEDOAR’s α/β(CBEDOAR’s α/β) in each voxel of critical OARs is calculated by changing the number of fractions in a stepwise process. The most appropriate prescribing absorbed dose to the target and the number of fractions in reirradiation is determined by using CBEDOAR’s α/β-volume histogram for critical OARs. The function of the tool was validated in silico using 3 scenarios in 2 patients: a patient with a lung cancer at the peripheral lung parenchyma and at the hilar lymphatic region at different times, and in a patient with a metastatic internal mammary lymph node relapsed after postoperative radiation therapy for breast cancer.
Results
In scenario 1, giving 57 Gy in 22 fractions (57 Gy/22 Fr) to the CTV2 at the right hilum, the maximum CBEDα/β=2 was 124.078 Gy, and the mean CBEDα/β=2 of the whole lung parenchyma excluding gross tumor volume was 18.332 Gy. In scenario 2, 44.152 Gy/7 Fr to the target was suggested to be most appropriate. In scenario 3, 71.675 Gy/30 Fr proton therapy to the target was recommended in which the maximum CBEDα/β=2 in the aorta near the recurrence site was 145.796 Gy, and the volume of CBEDα/β=2 ≥ 100 Gy was 0.800 cm3, both are within the constraints.
Conclusions
The tool was suggested to be useful to find the most appropriate prescribing absorbed dose to the target as well as the number of fractions for precise reirradiation., 46173522 - Deep learning-based imaging analysis reveals radiation-induced bystander effects on cancer cell migration and the modulation by cisplatin.
Ryosuke Seino, Hisanori Fukunaga
International Journal of Molecular Sciences, 26, 16, 7822, 2025年08月13日, [査読有り], [最終著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Regulating tumor invasion and metastasis is pivotal for improving cancer patient prognosis. While cell migration is a key factor in these processes, the non-targeted effects of chemoradiotherapy on cell motility remain poorly understood. In this study, we employed HeLa-FUCCI cells—a cervical cancer-derived HeLa cell line integrated with the Fluorescent Ubiquitination-Based Cell Cycle Indicator (FUCCI) probe, enabling the visualization of cell cycle phases—to investigate the radiation-induced impacts, including non-targeted effects, on cell migration. To create irradiated (In-field) and non-irradiated (out-of-field) regions, half of the culture dish was shielded with a lead block during irradiation. Cells were then exposed to 2 Gy X-rays, with or without cisplatin. Following irradiation, the cells were subjected to time-lapse imaging at 15 min intervals for 24 h, and the acquired data were analyzed using cell segmentation and tracking algorithms, Cellpose 2.0 and TrackMate 7. Without cisplatin, the migration velocity and total distance traveled of Out-of-field cells were significantly reduced compared to controls, suggesting a suppressive bystander signal. In contrast, with cisplatin treatment, these parameters significantly increased in both In-field and Out-of-field cells. This suggests that chemoradiotherapy may inadvertently enhance tumor cell motility outside the target volume, a critical finding with significant implications for therapeutic outcomes., 35821660 - Cell cycle- and dose-dependent effects on mitochondrial DNA copy number variation following irradiation.
Ryosuke Seino, Kai Nishikubo, Hisanori Fukunaga
Journal of Cell Science, 138, 15, jcs263642, 2025年08月08日, [査読有り], [最終著者, 責任著者], [国際誌]
日本語, 研究論文(学術雑誌), Cell survival after irradiation depends on the cell cycle at the time of exposure. This has been thought to be due to cell cycle-dependent nuclear DNA damage repair mechanisms. Here we show the relationships between the exposed dose, the cell cycle phase at the time of exposure, and changes in mitochondrial DNA copy numbers (mtDNAcn) after irradiation. We used a fluorescent ubiquitination-based cell cycle indicator (FUCCI), which allows visualization of the cell cycle, and confirmed cell cycle synchronization in human cervical HeLa cells. In synchronous HeLa-FUCCI cells, the mtDNAcn changed with the progression of the cell cycle. Also, G1 phase-synchronized cells showed a dose-dependent increase of mtDNAcn at 48 h after X-ray exposure, while G2 cells showed a dose-dependent increase at 24 h. In addition, S phase-synchronized cells showed a dose-dependent increase at 24 and 48 h after irradiation. These results showed the cell cycle- and dose-dependent effects on mtDNAcn after irradiation, which may shed light on the emerging role of mitochondrial genome and in cell survival. - Time-lapse imaging of cells in spatially fractionated X-ray fields using a mini beam as an alternative to accelerator-based sub-millimeter beams.
Kiichi Kaminaga, Hisanori Fukunaga, Eri Hirose, Ritsuko Watanabe, Keiji Suzuki, Kevin M Prise, Akinari Yokoya
Journal of Radiation Research, 66, 3, 318, 328, Oxford University Press (OUP), 2025年05月11日, [査読有り], [国際共著], [国際誌]
英語, 研究論文(学術雑誌), Due to the limited number of accelerator-based X-ray facilities worldwide that provide beams with an adjustable size, their application for radiobiological research purposes has been restricted. Thus, the development of alternative methods is of technical importance for investigating cell/tissue responses in spatially non-uniform radiation fields. In this study, we performed mini beam irradiation of cells using a lead (Pb) sub-milli-collimator as an alternative method to sub-millimeter beams. Also, we employed human cervical carcinoma HeLa cells and hTERT-immortalized fibroblast BJ-1 cells that express fluorescence ubiquitination-based cell-cycle indicators (FUCCI). Time-lapse imaging revealed differences in the behavior of HeLa and BJ-1 cells in spatially heterogeneous radiation fields; in the case of HeLa cells, G2/M phase-arrested cells in the cell population were clearly observed, distinguishing irradiated from non-irradiated cells at the sub-millimeter scale level. Our findings indicate that FUCCI can be useful as a biological dose indicator, depending on cell type, and Pb sub-milli-collimators show potential as a possible alternative to accelerator-based X-ray sub-millimeter beams for radiobiological research. The use of the collimators, unlike beamtime experiments in synchrotron facilities with the approval of the committee, is highly versatile and may be beneficial in preliminary studies in a normal laboratory environment., 12864138 - Mitochondrial DNA copy numbers in gastric cancer tissues: a possible biomarker for estimating cancer progression.
Hisanori Fukunaga, Mayuko Fukunaga
Japanese Journal of Clinical Oncology, 55, 8, 920, 924, Oxford University Press (OUP), 2025年04月23日, [査読有り], [筆頭著者, 責任著者], [国際誌]
日本語, 研究論文(学術雑誌), Background
Mitochondria have their own genome (mtDNA), which in humans is a circular multi-copy genome consisting of 16 569 base pairs. Abnormalities in the mtDNA have been reported to correlate with various age-related pathophysiologies.
Methods
Based on a total of 182 DNA samples extracted from gastric cancer tissues, we measured mtDNA copy numbers (mtDNA-CN) using real-time polymerase chain reaction (PCR) and then examined alongside sex, age, tumor stage, Laurén classification, and the overexpression of Human Epidermal Growth Factor Receptor 2 (HER2).
Results
We found no sex differences in mtDNA-CN and no correlation with age, but significant differences according to tumor stage. The mtDNAcn of intestinal type by Laurén classification was significantly larger than that of diffuse type. There was no significant difference in mtDNA-CN between HER2-positive and -negative tissues. Multiple regression analyses showed that only the tumor stage was a significant variable, while Laurén classification was not.
Conclusion
These results indicate that mitochondrial genomic abnormalities contribute the progression of gastric cancer independently of HER2 overexpression, and may shed light on the emerging role of mtDNA-CN in situ as a possible biomarker for estimating cancer progression. - 放射線に関する知識と不安: 一般土木建設工事業従事者と診療放射線技師を対象としたオンライン調査
阿部 紀宜, 清野 良輔, 池田 敦子, 福永 久典
保健物理, 60, 1, 48, 54, 日本保健物理学会, 2025年03月, [査読有り], [最終著者, 責任著者], [国内誌]
日本語, 研究論文(学術雑誌), * 公益社団法人日本放射線技術学会 北海道支部 第80回秋季大会優秀研究賞 受賞
In this study, by using an online survey, we obtained responses regarding basic knowledge of radiation and anxiety associated with radiation exposure from 500 general construction workers, who are likely to be engaged in decontamination work after a nuclear disaster or radiation accident, and 200 radiological technologists, who have expertise in the biological effects and clinical applications of radiation. A chi-square test showed significant differences in the groups’ basic knowledge of radiation; the degree of anxiety about radiation exposure was significantly greater among general construction workers than among radiological technologists. In addition, a logistic regression analysis revealed a significant correlation between knowledge of “the difference between natural and artificial radiation” and “the difference between internal and external exposure” and anxiety associated with radiation exposure. Taken together, our findings suggest that appropriate radiation education may contribute to reducing anxiety associated with radiation exposure., 35821660 - チューブリン重合反応に対するX線影響の検討—インビトロ再構成実験系を用いたアプローチ—
阿部 紀宜, 清野 良輔, 横谷 明徳, 福永 久典
RADIOISOTOPES, 74, 1, 103, 108, Japan Radioisotope Association, 2025年02月15日, [査読有り], [最終著者, 責任著者], [国際誌]
日本語, 研究論文(学術雑誌), * 第29回RADIOISOTOPES誌論文奨励賞 受賞
細胞質に存在する微小管は,細胞の構造維持と機能発現において重要な役割を果たしている。しかし,αβ-チューブリンヘテロ二量体からなる微小管に及ぼす放射線影響は依然として十分に明らかではない。本研究では,放射線被ばくによって損傷したチューブリンが,その重合反応に与える影響を明らかにするために,蛍光チューブリン重合アッセイキットを用いて,in vitro重合反応におけるX線被ばくチューブリンと非照射チューブリンの相互作用を調べた。その結果,X線照射されたチューブリンは微小管を形成することはできないが,正常チューブリンの重合反応に寄与する可能性が示唆された。, 40580887 - Radiation-induced impacts on mitochondrial DNA and the transgenerational genomic instability.
Ryosuke Seino, Haruka Kubo, Kai Nishikubo, Hisanori Fukunaga
Environment International, 196, 109315, Elsevier BV, 2025年02月02日, [査読有り], [最終著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Background
Mitochondrial genomes are dynamically evolving and are shaped by somatic mutation and selection throughout the female germline. In this study, we investigated the radiation-induced impacts on mitochondrial DNA in vitro and in vivo, as well as the transgenerational inheritance.
Methods
Human cervical cancer HeLa cells and telomerase-immortalized normal fibroblast BJ1-hTERT cells were exposed to X-rays at 0.5–8 Gy. Also, we exposed 8-week-old female C57BL/6N mice to a single whole-body dose of 2 Gy of X-rays and mated them with healthy males 1 day after irradiation. We extracted DNA from the irradiated cells, female mice, and the 2-week-old pups, then examined the mitochondrial DNA copy numbers (mtDNAcns) and radiation-induced damage by real-time quantitative PCR.
Results
The mtDNAcn levels in cells increased and the intact copy ratios decreased 24 h after irradiation, resulting in the delayed shift of heteroplasmy. Also, the peripheral blood-derived mtDNAcn levels in irradiated females increased 1 day after irradiation and the intact copy rates decreased, supporting the results in vitro. Furthermore, whole blood-derived mtDNAcn levels decreased in 2-week-old pups born from irradiated mothers, indicating the mitochondrial genomic instability.
Discussion
We found the delayed induction of mtDNA damage in human cancer and noncancerous cells after irradiation, as well as the same trend in mice. Furthermore, to our knowledge, this is first to demonstrate the hereditary effects of radiation on the regulation of mitochondrial genome. These provide novel insights into the significance of radiation protection and preventive medicine for not only pre-pregnancy females but also the next generation. - Testicular exposure to ionizing radiation and sperm epigenetic alterations as possible mechanisms of hereditary effects: perspectives from the viewpoint of radiation protection.
Hisanori Fukunaga, Nobuyuki Hamada
International Journal of Radiation Biology, 101, 2, 101, 106, Informa UK Limited, 2025年02月, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Purpose: Since the genotoxicity of ionizing radiation was demonstrated in the 1920s, its hereditary effects have remained a serious concern for human society. The International Commission on Radiological Protection has highlighted the need for appropriate protection against hereditary effects of radiation in humans. In this paper, we review the literature on the possible multigenerational and transgenerational effects following testicular exposure to radiation, focusing on sperm epigenetic alterations as possible mechanisms.
Results: This mini-review highlights that hereditary effects following testicular exposure occur via epigenetic changes of germ cells in animal models, providing implications on human radiation protection.
Conclusions: A great amount of epigenomic research data has emerged rapidly since the beginning of this century; thus, a revision of the radiological protection protocols against the hereditary effects of radiation would be no longer inevitable. The collection and analysis of evidence on these effects must be enhanced and further accelerated to formulate appropriate protection protocols in the future.
Keywords: Epigenetic; ionizing radiation; multigenerational; spermatogenesis; transgenerational. - Mitochondrial DNA copy number variations in Epstein-Barr virus-transformed B cells after exposure to radiation: A possible biomarker for dose assessment.
Hitomi Muramatsu, Ryosuke Seino, Hisanori Fukunaga
Biomedical Research, 46, 1, 9, 14, Biomedical Research Press, 2025年01月31日, [査読有り], [最終著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Following accidental radiation exposure due to a radiological or nuclear emergency, a dose assessment should be performed based on biological samples from exposed individuals. Although previous biological dose assessment approaches have focused on nuclear DNA damage in peripheral lymphocytes, this study investigated the radiation-induced impact on the mitochondrial genome, particularly the chronological changes in the mitochondrial DNA copy number (mtDNAcn) following exposure to radiation. We used B-lymphoblastoid cell lines transformed by Epstein-Barr virus established from 12 healthy individuals in their 20s (six males, six females) with or without a history of smoking. Using real-time quantitative PCR, we determined the mtDNAcn from the B cells cultured for 6, 24, and 96 h and after exposure to 0, 1, 2, and 4 Gy X-rays. We found a significant relationship between the exposed dose and mtDNAcn in the 96-hour post-irradiation cells for non-smoking males, suggesting the possible role of mtDNAcn as a biomarker for dose assessment. - Reply to Comments on 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation'.
Yuta Shiraishi, Yusuke Matsuya, Hisanori Fukunaga
Physics in Medicine & Biology, 69, 248002, IOP Publishing, 2024年12月12日, [査読有り], [招待有り], [最終著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Liew and Mairani (2024 Phys. Med. Biol. 69 248001) commented on our previous reply to comments on our paper, 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation'. We appreciate their comments on the choice of experimental data on DNA damage for cell survival and agree that the estimate of the dose-response curve on cell survival depends on the selection of DNA damage data. As an additional benchmark test, we compared the relative biological effectiveness (RBE) predicted using the recommended DNA damage data measured in normoxia with those reported in our original paper, and confirmed that the difference in RBE was less than 8%. Although our model allows for the estimation of cell survival and RBE under ultra-high dose rate (UHDR) irradiation, we highlight that a further accumulation of experimental data on DNA damage under UHDR irradiation is necessary for the further development of biophysical models concerning the mechanistical estimation of biological effects. - Random threshold model: A low-dose radiation-induced risk assessment approach considering individual susceptibility to cancer.
Takashi Yanagawa, Hisanori Fukunaga
Dose-Response, 22, 4, 15593258241298553, 2024年11月03日, [査読有り], [最終著者], [国際誌]
英語, 研究論文(学術雑誌), Objectives: The linear no-threshold (LNT) model, which has been used for radiation protection purposes, was developed based on the assumption that exposure to even a small amount of radiation may cause cancer. However, although it is known in carcinogenesis that there is variation in radiation sensitivity among individuals, the LNT model does not adequately consider radiosensitive subgroups. In this paper, we represent susceptibility to contract cancer by radiation exposure by means of the threshold of a dose-response function, introduce an assumption that the thresholds are random to represent the variation of the radiosensitivity among individuals in a susceptible subgroup. We propose a novel method, the random threshold (RT) model, for determining the safe dose limit for the subgroup to protect cancer-susceptible individuals from radiation exposure. Conclusion: The proposed method is illustrated by targeting ATM gene (a cancer-susceptible gene) mutation carriers as a radiosensitive subgroup. For cancer risk associated with low-dose radiation exposure, the contribution of radiosensitivity cannot be ignored, thus the RT model would be more suitable for risk protection for radiosensitive subgroups instead of the LNT model. We also notice that it could be widely applicable for risk protection of not only low-dose radiation but also environmental pollutants., 35821660 - Cell-cycle dependence on the biological effects of boron neutron capture therapy and its modification by polyvinyl alcohol.
Yusuke Matsuya, Tatsuhiko Sato, Tamon Kusumoto, Yoshie Yachi, Ryosuke Seino, Misako Miwa, Masayori Ishikawa, Shigeo Matsuyama, Hisanori Fukunaga
Scientific Reports, 14, 1, 16696, Springer Science and Business Media LLC, 2024年07月19日, [査読有り], [最終著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Boron neutron capture therapy (BNCT) is a unique radiotherapy of selectively eradicating tumor cells using boron compounds (e.g., 4-borono-l-phenylalanine [BPA]) that are heterogeneously taken up at the cellular level. Such heterogenicity potentially reduces the curative efficiency. However, the effects of temporospatial heterogenicity on cell killing remain unclear. With the technical combination of radiation track detector and biophysical simulations, this study revealed the cell cycle-dependent heterogenicity of BPA uptake and subsequent biological effects of BNCT on HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators, as well as the modification effects of polyvinyl alcohol (PVA). The results showed that the BPA concentration in the S/G2/M phase was higher than that in the G1/S phase and that PVA enhances the biological effects both by improving the uptake and by canceling the heterogenicity. These findings might contribute to a maximization of therapeutic efficacy when BNCT is combined with PVA and/or cell cycle-specific anticancer agents., 36092723 - Evaluation of Cell Cycle-Dependent Migration Activity after X-ray Exposure: A Radiobiological Approach for Optimization of Radiotherapy with Cell Cycle-Targeting Agents.
Ryosuke Seino, Hisanori Fukunaga
Radiation Research, 202, 1, 87, 95, Radiation Research Society, 2024年07月, [査読有り], [最終著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Radiotherapy with cell cycle-specific anticancer agents has become an important option in the control of both primary tumors and metastases. Here, we used image analysis algorithms that enable quick segmentation and tracking to describe a radiobiological approach for the optimized selection of cell cycle-targeting anticancer drugs for radiotherapy. We confirmed cell cycle-synchronization using human cervical cancer HeLa cells expressing a fluorescent ubiquitination-based cell cycle indicator (FUCCI) as a cell cycle-monitoring probe. Cells synchronized in the G1 and G2 phases were irradiated with X rays at 0.5–2 Gy. Each cell was identified using Cellpose, a deep learning-based algorithm for cellular segmentation, and the velocity and direction of migration were analyzed using the TrackMate plugin in Fiji ImageJ. G1 phase synchronized cells showed a dose-dependent decrease in velocity after irradiation, while G2 cells tended to increase their velocity. The migration pattern of all cells appeared to be a random walk model, regardless of the exposure dose. In addition, we used cisplatin to arrest the cell cycle. HeLa-FUCCI cells arrested at the G2 phase via cisplatin treatment showed enhanced cell migration after X-ray exposure. These results indicated that anticancer agents that arrest the cell cycle of cancer cells in a specific phase may enhance cell migration after radiotherapy. Our approach, using cellular segmentation and tracking algorithms, could enhance the radiobiological assessment of cell cycle-specific migration after irradiation to aid in optimizing radiotherapy using cell cycle-targeting agents., 35821660 - How does formal and informal industry contribute to lead exposure? A narrative review from Vietnam, Uruguay, and Malaysia.
Kritika Poudel, Atsuko Ikeda, Hisanori Fukunaga, Marie-Noel Brune Drisse, Lesley Jayne Onyon, Julia Gorman, Amalia Laborde, Reiko Kishi
Reviews on Environmental Health, 39, 2, 371, 388, 2024年06月05日, [査読有り], [国際誌]
英語, 研究論文(学術雑誌) - Reply to Comment on 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation'.
Yuta Shiraishi, Yusuke Matsuya, Hisanori Fukunaga
Physics in Medicine & Biology, 69, 108002, IOP Publishing, 2024年04月15日, [査読有り], [招待有り], [最終著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Liew and Mairani commented on our paper 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation' (Shiraishi et al 2024a Phys. Med. Biol.69 015017), which proposed a biophysical model to predict the dose–response curve of surviving cell fractions after ultra-high dose rate irradiation following conventional dose rate irradiation by considering DNA damage yields. They suggested the need to consider oxygen concentration in our prediction model and possible issues related to the data selection process used for the benchmarking test in our paper. In this reply, we discuss the limitations of both the present model and the available experimental data for determining the model's parameters. We also demonstrate that our proposed model can reproduce the experimental survival data even when using only the experimental DNA damage data measured reliably under normoxic conditions. - X線被ばく後の細胞接着面積の変化と細胞周期依存性 ―深層学習に基づく画像解析の放射線生物学への応用―
清野 良輔, 福永 久典
RADIOISOTOPES, 73, 1, 61, 67, 日本アイソトープ協会, 2024年03月15日, [査読有り], [最終著者, 責任著者], [国内誌]
日本語, 研究論文(学術雑誌), 近年,深層学習を用いた画像解析が注目されている。放射線生物学分野への応用可能性の検討を目的として,本研究では深層学習に基づく細胞セグメンテーションアルゴリズムCellpose 2.0を用いて,細胞周期を同調させたヒト子宮頸がん由来HeLa細胞において放射線被ばく後の細胞接着面積の変化を詳細に解析した。その結果,G1期細胞ではX線被ばく後に細胞接着面積が増加するのに対し,G2期細胞では減少することを新たに見出した。今後,このような人工知能利用による放射線生物学研究のさらなる進展が期待される。, 35821660 - Cell Cycle Dependence of Cell Survival following Exposure to X-rays in synchronous HeLa Cells expressing Fluorescent Ubiquitination-based Cell Cycle Indicators.
Ryosuke Seino, Hiroto Uno, Kevin M Prise, Hisanori Fukunaga
Biomedical Research, 45, 1, 25, 31, Biomedical Research Press, 2024年02月02日, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), The cell cycle dependence of radiosensitivity has yet to be fully determined, as it is technically difficult to achieve a high degree of cell cycle synchronization in cultured cell systems and accurately detect the cell cycle phase of individual cells simultaneously. We used human cervical carcinoma HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators (FUCCI), and employed the mitotic harvesting method that is one of the cell cycle synchronization methods. The imaging analysis confirmed that the cell cycle is highly synchronized after mitotic cell harvesting until 18-20 h of the doubling time has elapsed. Also, flow cytometry analysis revealed that the S and G2 phases peak at approximately 12 and 14-16 h, respectively, after mitotic harvesting. In addition, the clonogenic assay showed the changes in surviving fractions following exposure to X-rays according to the progress through the cell cycle. These results indicate that HeLa-FUCCI cells become radioresistant in the G1 phase, become radiosensitive in the early S phase, rapidly become radioresistant in the late S phase, and become radiosensitive again in the G2 phase. Our findings may contribute to the further development of combinations of radiation and cell cycle-specific anticancer agents., 35821660 - Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation.
Yuta Shiraishi, Yusuke Matsuya, Tamon Kusumoto, Hisanori Fukunaga
Physics in Medicine & Biology, 69, 1, 015017, IOP Publishing, 2024年01月07日, [査読有り], [最終著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Objective. FLASH radiotherapy (FLASH-RT) with ultra-high dose rate (UHDR) irradiation (i.e. > 40 Gy s−1) spares the function of normal tissues while preserving antitumor efficacy, known as the FLASH effect. The biological effects after conventional dose rate-radiotherapy (CONV-RT) with ≤0.1 Gy s−1 have been well modeled by considering microdosimetry and DNA repair processes, meanwhile modeling of radiosensitivities under UHDR irradiation is insufficient. Here, we developed an integrated microdosimetric-kinetic (IMK) model for UHDR-irradiation enabling the prediction of surviving fraction after UHDR irradiation. Approach. The IMK model for UHDR-irradiation considers the initial DNA damage yields by the modification of indirect effects under UHDR compared to CONV dose rate. The developed model is based on the linear-quadratic (LQ) nature with the dose and dose square coefficients, considering the reduction of DNA damage yields as a function of dose rate. Main results. The estimate by the developed model could successfully reproduce the in vitro experimental dose–response curve for various cell line types and dose rates. Significance. The developed model would be useful for predicting the biological effects under the UHDR irradiation. - Possible mechanisms and simulation modeling of FLASH radiotherapy.
Yuta Shiraishi, Yusuke Matsuya, Hisanori Fukunaga
Radiological Physics and Technology, 17, 11, 23, Springer Science and Business Media LLC, 2024年01月06日, [査読有り], [最終著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), FLASH radiotherapy (FLASH-RT) has great potential to improve patient outcomes. It delivers radiation doses at an ultra-high dose rate (UHDR: ≥ 40 Gy/s) in a single instant or a few pulses. Much higher irradiation doses can be administered to tumors with FLASH-RT than with conventional dose rate (0.01-0.40 Gy/s) radiotherapy. UHDR irradiation can suppress toxicity in normal tissues while sustaining antitumor efficiency, which is referred to as the FLASH effect. However, the mechanisms underlying the effects of the FLASH remain unclear. To clarify these mechanisms, the development of simulation models that can contribute to treatment planning for FLASH-RT is still underway. Previous studies indicated that transient oxygen depletion or augmented reactions between secondary reactive species produced by irradiation may be involved in this process. To discuss the possible mechanisms of the FLASH effect and its clinical potential, we summarized the physicochemical, chemical, and biological perspectives as well as the development of simulation modeling for FLASH-RT. - Mitochondrial DNA copy number variation across three generations: A possible biomarker for assessing perinatal outcomes.
Hisanori Fukunaga, Atsuko Ikeda
Human Genomics, 17, 1, 113, Springer Science and Business Media LLC, 2023年12月15日, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Background: Mitochondria have their own circular multi-copy genome (mtDNA), and abnormalities in the copy number are implicated in mitochondrial dysfunction, which contributes to a variety of aging-related pathologies. However, not much is known about the genetic correlation of mtDNA copy number across multiple generations and its physiological significance.
Methods: We measured the mtDNA copy number in cord blood or peripheral blood from 149 three-generation families, specifically the newborns, parents, and grandparents, of 149 families, totaling 1041 individuals. All of the biological specimens and information were provided by the Tohoku Medical Megabank Project in Japan. We also analyzed their maternal factors during pregnancy and neonatal outcomes.
Results: While the maternal peripheral blood mtDNA copy number was lower than that of other adult family members, it was negatively correlated with cord blood mtDNA copy number in male infants. Also, cord blood mtDNA copy numbers were negatively correlated with perinatal outcomes, such as gestation age, birth weight, and umbilical cord length, for both male and female neonates. Furthermore, the mtDNA copy number in the infants born to mothers who took folic acid supplements during pregnancy would be lower than in the infants born to mothers who did not take them.
Conclusions: This data-driven study offers the most comprehensive view to date on the genetic and physiological significance of mtDNA copy number in cord blood or peripheral blood taken from three generations, totaling more than 1000 individuals. Our findings indicate that mtDNA copy number would be one of the transgenerational biomarkers for assessing perinatal outcomes, as well as that appropriate medical interventions could improve the outcomes via quantitative changes in mtDNA.
Keywords: Birth cohort; Cord blood; DNA copy number variation; Maternal exposure; Mitochondrial DNA., 32502774 - Validation of mitotic harvesting method with human cervical carcinoma HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators for radiation research.
Ryosuke Seino, Hiroto Uno, Hisanori Fukunaga
Biomedical Research, 44, 5, 181, 186, Biomedical Research Press, 2023年09月27日, [査読有り], [最終著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), The cell cycle is a series of events in the process of one cell giving rise to two daughter cells. The mitotic harvesting method, established by Terasima and Tolmach in the 1960s, causes minimal physiological stress on the cells and achieves a high degree of cell cycle synchrony by collecting only mitotic cells from a cultured cell system. The purpose of the present study is to validate the versatility of the mitotic harvesting method using human cervical cell line HeLa cells expressing Fluorescent Ubiquitination-based Cell Cycle Indicators (FUCCI) and to estimate the cell cycle-dependent changes in radiosensitivity in HeLa–FUCCI cells. The image analysis showed that cell cycle synchrony was maintained for at least 24 hours after mitotic cell collection. Also, the clonogenic assay demonstrated changes in radiosensitivity that were cell cycle dependent. These results indicate that the mitotic harvesting method using FUCCI-expressing cells has high versatility in the field of radiation cell biology., 35821660 - An Analytical Method for Quantifying the Yields of DNA Double-Strand Breaks Coupled with Strand Breaks by γ-H2AX Focus Formation Assay Based on Track-Structure Simulation.
Yoshie Yachi, Yusuke Matsuya, Yuji Yoshii, Hisanori Fukunaga, Hiroyuki Date, Takeshi Kai
International Journal of Molecular Sciences, 24, 2, 1386, 2023年01月10日, [査読有り], [国際誌]
英語, 研究論文(学術雑誌), Complex DNA double-strand break (DSB), which is defined as a DSB coupled with additional strand breaks within 10 bp in this study, induced after ionizing radiation or X-rays, is recognized as fatal damage which can induce cell death with a certain probability. In general, a DSB site inside the nucleus of live cells can be experimentally detected using the γ-H2AX focus formation assay. DSB complexity is believed to be detected by analyzing the focus size using such an assay. However, the relationship between focus size and DSB complexity remains uncertain. In this study, using Monte Carlo (MC) track-structure simulation codes, i.e., an in-house WLTrack code and a Particle and Heavy Ion Transport code System (PHITS), we developed an analytical method for qualifying the DSB complexity induced by photon irradiation from the microscopic image of γ-H2AX foci. First, assuming that events (i.e., ionization and excitation) potentially induce DNA strand breaks, we scored the number of events in a water cube (5.03 × 5.03 × 5.03 nm3) along electron tracks. Second, we obtained the relationship between the number of events and the foci size experimentally measured by the γ-H2AX focus formation assay. Third, using this relationship, we evaluated the degree of DSB complexity induced after photon irradiation for various X-ray spectra using the foci size, and the experimental DSB complexity was compared to the results estimated by the well-verified DNA damage estimation model in the PHITS code. The number of events in a water cube was found to be proportional to foci size, suggesting that the number of events intrinsically related to DSB complexity at the DNA scale. The developed method was applicable to focus data measured for various X-ray spectral situations (i.e., diagnostic kV X-rays and therapeutic MV X-rays). This method would contribute to a precise understanding of the early biological impacts of photon irradiation by means of the γ-H2AX focus formation assay., 36662431 - A brief overview of the registration system of radiation exposure doses for decontamination workers and their occupational health management.
Hisanori Fukunaga, Tomohiro Asano
Journal of Occupational Health, 64, 1, e12357, Japan Society for Occupational Health, 2022年09月08日, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Following the Fukushima nuclear accident in March 2011, decontamination and related works have been carried out over a wide area, mainly in Fukushima Prefecture. In November 2013, the Radiation Dose Registration and Management System for Decontamination Workers was established to manage the occupational exposure doses of workers engaged in such work. The Radiation Effects Association mainly operates the registration system. This paper summarizes existing reports on this system and occupational health issues among decontamination workers. We collected previous reports and related regulatory laws on occupational health management for decontamination workers working in Fukushima Prefecture, summarized the outline of the radiation dose registration and management system for these decontamination workers, and discussed future issues related to their health management. Approximately 100 000 decontamination workers were registered in the system as of 2020, but none showed radiation doses that exceeded the dose limit. To our knowledge, there have been no reports of decontamination workers presenting physical symptoms suspected to be related to radiation exposure. On the other hand, heatstroke countermeasures and anxiety about radiation exposure have been reported as possible issues in the occupational health management of decontamination workers. Although decontamination workers are unlikely to experience biological effects from radiation exposure, epidemiological studies are needed to examine this evidence. Further analysis is also needed on non-radiation effects, which pose occupational health concerns for decontamination workers. The registration system would allow for tracking decontamination workers, providing data for analyzing radiological and non-radiological effects., 35821660 - Narrative review of lead poisoning in humans caused by industrial activities and measures compatible with sustainable industrial activities in Republic of Zambia.
Hokuto Nakata, Shouta M.M. Nakayama, John Yabe, Kaampwe Muzandu, Andrew Kataba, Atsuko Ikeda-Araki, Marie-Noel Brune Drisse, Lesley Jayne Onyon, Julia Gorman, Poudel Kritika, Hisanori Fukunaga, Yoshinori Ikenaka, Reiko Kishi, Mayumi Ishizuka
Science of The Total Environment, 850, 157833, Elsevier BV, 2022年08月, [査読有り], [国際共著], [国際誌]
英語, 研究論文(学術雑誌), Lead (Pb) pollution and human exposure to Pb, is an important issue for the international community to address being associated with 0.90 million deaths from long-term effects. The Republic of Zambia is a typical mineral resource-rich country, with long-standing mining and smelting activities of metals including Pb in several parts of the country. This narrative review provides a comprehensive overview of previous papers that have assessed human exposure to Pb and related health effects in Zambia. Environmental remediation methods that should be applied locally, ways to reduce Pb exposure of the population, and issues that need to be addressed by various sectors are discussed. Environmental remediation methods using locally available and affordable materials are needed to ensure both sustainable industrial activities and pollution prevention. In the Zambian mining towns, including Kabwe, various research activities have been conducted, including environmental monitoring, human biomonitoring and health impact assessments. The town of Kabwe, which was one of Zambia's largest Pb mining area in the 20th century, continues to have formal and informal Pb-related industries and is known as one of the most polluted areas in the world. For example, despite the World Health Organization asserting that “For an individual with a blood Pb concentration ≥ 5 μg/dL, appropriate action should be taken to terminate exposure”, there are reports of blood Pb levels in Kabwe children exceeding 100 μg/dL. While Pb pollution is a global issue, not many places have such continuous and comprehensive research has been conducted, and there is much to be learned from the knowledge accumulated in these areas. Because the high levels of Pb accumulation in humans and the adverse health effects were clarified, we consider that it is important to combine mining activities, which are a key industry, with measures to prevent environmental pollution. - Molecular Interactions of Normal and Irradiated Tubulins During Polymerization.
Hisanori Fukunaga, Yuka Kimura, Ami Suzuki, Yuki Kawabata, Akinari Yokoya
Radiation Research, 198, 2, 200, 203, Radiation Research Society, 2022年08月, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Microtubules, one of the cytoskeletons, are highly dynamic structures that play a variety of roles in maintaining cell morphology, cell division and intracellular transport. Microtubules are composed of heterodimers of α- and β-tubulins, which are repeatedly polymerized and depolymerized. To investigate the radiation-induced impacts on the polymerization reaction of tubulins, we evaluated the molecular interactions between normal and irradiated tubulins. First, the polymerization reaction of the tubulins was measured after stepwise irradiation from 0 Gy to 1,000 Gy of X rays. The polymerization was inhibited in a dose-dependent manner. Next, the tubulins' polymerization reaction was then measured after the tubulin that was damaged from the exposure to 1,000 Gy of X rays was mixed with the normal tubulins. Our findings reveal that the radiation dose-dependent change in the degree of overall microtubule polymerization progression depends on the ratio of damaged tubulin. This result is biochemical evidence that non-DNA damage (in this case, cytoskeletal damage) from cytoplasmic radiation exposure may inhibit cell division, suggesting that some cytoskeletal damage may also affect the fate of the entire cell., 13377196 - マウス精巣器官培養法を活用した放射線不妊メカニズムの解析
神長 輝一, 横谷 明徳, 福永 久典
RADIOISOTOPES, 71, 1, 35, 40, 日本アイソトープ協会, 2022年03月15日, [査読有り], [最終著者, 責任著者], [国内誌]
日本語, 研究論文(学術雑誌), (第26回RADIOISOTOPES誌論文奨励賞 受賞論文)
放射線治療における妊孕性の保護は、がん患者の治療後の生活にとって、重要な意義をもつ。本研究では、マウス精巣器官培養法と一般的なX線照射装置を組み合わせて、空間的に不均一な放射線場における精子形成能の損傷と回復の過程を解析したところ、生殖幹細胞の移動が回復過程に関与している可能性が示唆された。今後、このような組織培養アプローチを用いた放射線不妊メカニズム研究の発展と普及が期待される。 - Features of accelerator-based neutron source for boron neutron capture therapy calculated by particle and heavy ion transport code system (PHITS).
Yusuke Matsuya, Tamon Kusumoto, Yoshie Yachi, Yuho Hirata, Misako Miwa, Masayori Ishikawa, Hiroyuki Date, Yosuke Iwamoto, Shigeo Matsuyama, Hisanori Fukunaga
AIP Advances, 12, 2, 025013, AIP Publishing, 2022年02月10日, [査読有り], [最終著者], [国際誌]
英語, 研究論文(学術雑誌), Accelerator-based neutron sources have been developed and installed in recent decades for boron neutron capture therapy (BNCT) in several clinical facilities. Lithium is one of the targets that can produce epithermal neutrons from the 7Li(p,n)7Be near-threshold reaction, and accelerator-based BNCT systems employing a Li target are promising for cancer treatment. The accurate evaluation of the characteristics of an accelerator-based neutron source is a key to estimating the therapeutic effects of the accelerator-based BNCT. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo code, which can simulate a variety of diverse particle types and nuclear reactions. The latest PHITS code enables simulating the generation of neutrons from the 7Li(p,n)7Be reactions by using the Japanese Evaluated Nuclear Data Library 4.0 high-energy file. Thus, the PHITS code can be adopted for dose estimation during treatment planning for the accelerator-based BNCT. In this study, we evaluated the neutron fluence using the PHITS code by comparing it to reference data. The subsequent neutron transport simulations were performed to evaluate the boron trifluoride detector responses and the recoiled proton fluence detected by a CR-39 plastic detector. These comparative studies confirmed that the PHITS code can accurately simulate neutrons generated from an accelerator using a Li target. The PHITS code has a significant potential for a detailed evaluation of neutron fields and for predicting the therapeutic effects of the accelerator-based BNCT., 36092723 - A Brief Overview of Radiation-Induced Effects on Spermatogenesis and Oncofertility.
Hisanori Fukunaga, Akinari Yokoya, Kevin M. Prise
Cancers, 14, 3, 805, MDPI AG, 2022年02月04日, [査読有り], [招待有り], [筆頭著者, 責任著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌), The genotoxicity of radiation on germ cells may be passed on to the next generation, thus its elucidation is not only a scientific issue but also an ethical, legal, and social issue in modern society. In this article, we briefly overview the effects of radiation on spermatogenesis and its associated genotoxicity, including the latest findings in the field of radiobiology. The potential role of transgenerational effects is still poorly understood, and further research in this area is desirable. Furthermore, from the perspective of oncofertility, we discuss the historical background and clinical importance of preserving male fertility during radiation treatment and the potential of microbeam radiotherapy. We hope that this review will contribute to stimulating further discussions and investigations for therapies for pediatric and adolescent/young adult patients. - Stem Cell Migration: A Possible Mechanism for the Tissue-Sparing Effect of Spatially Fractionated Radiation.
Hisanori Fukunaga
Radiation Research, 196, 6, 680, 685, Radiation Research Society, 2021年12月, [査読有り], [招待有り], [責任著者], [国際誌]
英語, 研究論文(学術雑誌), (Radiation Research Editors' Award 受賞研究解説)
Stem cell responses in tissues after exposure to radiation are of significance for maintaining tissue functions. From the point of view of stem cell characteristics, this article seeks to illustrate some contributions of microbeam research to spatially fractionated radiotherapy (SFRT), such as grid radiotherapy and microbeam radiotherapy. Although the tissue-sparing response after SFRT was first reported more than a century ago, current radiation dose-volume metrics are still unable to accurately predict such tissue-level changes in response to spatially fractionated radiation fields. However, microbeam approaches could contribute to uncovering the mechanisms of tissue response, significantly improving the outcomes of SFRT and reducing its adverse effects. Studies with microbeams have shown that the testicular tissue-sparing effect for maintaining spermatogenesis after exposure to spatially fractionated radiation depends on biological parameters, such as the radiation dose distribution at the microscale level for tissue-specific stem cells and the microenvironment, or niche. This indicates that stem cell survival, migration, and repopulation are involved in the tissue-level changes during or after SFRT. The illustration of microbeam applications in this article focuses on the stem cell migration as a possible mechanism of the tissue-sparing effect for preserving functionality. - No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields.
Hisanori Fukunaga, Kiichi Kaminaga, Eri Hirose, Ritsuko Watanabe, Noriko Usami, Kevin M. Prise, Akinari Yokoya
International Journal of Molecular Sciences, 22, 23, 12785, 2021年11月26日, [査読有り], [筆頭著者, 責任著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌), The non-targeted effects of radiation have been known to induce significant alternations in cell survival. Although the effects might govern the progression of tumor sites following advanced radiotherapy, the impacts on the intercellular control of the cell cycle following radiation exposure with a modified field, remain to be determined. Recently, a fluorescent ubiquitination-based cell-cycle indicator (FUCCI), which can visualize the cell-cycle phases with fluorescence microscopy in real time, was developed for biological cell research. In this study, we investigated the non-targeted effects on the regulation of the cell cycle of human cervical carcinoma (HeLa) cells
with imperfect p53 function that express the FUCCI (HeLa–FUCCI cells). The possible effects on the cell-cycle phases via soluble factors were analyzed following exposure to different field configurations, which were delivered using a 150 kVp X-ray irradiator. In addition, using synchrotron-generated, 5.35 keV monochromatic X-ray microbeams, high-precision 200 µm-slit microbeam irradiation was performed to investigate the possible impacts on the cell-cycle phases via cell–cell contacts. Collectively, we could not detect the intercellular regulation of the cell cycle in HeLa–FUCCI cells, which suggested that the unregulated cell growth was a malignant tumor. Our findings
indicated that there was no significant intercellular control system of the cell cycle in malignant tumors during or after radiotherapy, highlighting the differences between normal tissue and tumor characteristics. - A Brief Overview of the Preclinical and Clinical Radiobiology of Microbeam Radiotherapy.
Hisanori Fukunaga, Karl T. Butterworth, Stephen J. McMahon, Kevin M. Prise
Clinical Oncology, 33, 11, 705, 712, Elsevier BV, 2021年08月26日, [査読有り], [筆頭著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌), Microbeam radiotherapy (MRT) is the delivery of spatially fractionated beams that have the potential to offer significant improvements in the therapeutic ratio due to the delivery of micron-sized high dose and dose rate beams. They build on longstanding clinical experience of GRID radiotherapy and more recently lattice-based approaches. Here we briefly overview the preclinical evidence for MRT efficacy and highlight the challenges for bringing this to clinical utility. The biological mechanisms underpinning MRT efficacy are still unclear, but involve vascular, bystander, stem cell and potentially immune responses. There is probably significant overlap in the mechanisms underpinning MRT responses and FLASH radiotherapy that needs to be further defined. - Mitochondrial DNA Copy Number and Developmental Origins of Health and Disease (DOHaD).
Hisanori Fukunaga
International Journal of Molecular Sciences, 22, 12, 6634, MDPI AG, 2021年06月21日, [査読有り], [責任著者], [国際誌]
英語, 研究論文(学術雑誌), Mitochondrial dysfunction is known to contribute to mitochondrial diseases, as well as to a variety of aging-based pathologies. Mitochondria have their own genomes (mitochondrial DNA (mtDNA)) and the abnormalities, such as point mutations, deletions, and copy number variations, are involved in mitochondrial dysfunction. In recent years, several epidemiological studies and animal experiments have supported the Developmental Origin of Health and Disease (DOHaD) theory, which states that the environment during fetal life influences the predisposition to disease and the risk of morbidity in adulthood. Mitochondria play a central role in energy production, as well as in various cellular functions, such as apoptosis, lipid metabolism, and calcium metabolism. In terms of the DOHaD theory, mtDNA copy number may be a mediator of health and disease. This paper summarizes the results of recent epidemiological studies on the relationship between environmental factors and mtDNA copy number during pregnancy from the perspective of DOHaD theory. The results of these studies suggest a hypothesis that mtDNA copy number may reflect environmental influences during fetal life and possibly serve as a surrogate marker of health risks in adulthood., 32502774 - ホウ素中性子捕捉療法の治療効果予測モデルの開発
福永 久典, 松谷 悠佑
放射線生物研究, 56, 2, 208, 223, 放射線生物研究会, 2021年06月, [査読有り], [招待有り], [筆頭著者, 責任著者], [国内誌]
日本語, 研究論文(学術雑誌), ホウ素中性子捕捉療法(Boron Neutron Capture Therapy, BNCT)は、「腫瘍細胞選択的にホウ素薬剤を集積させ、10Bと熱中性子の核反応から生成される短飛程のα線やLiイオンを利用して、腫瘍細胞に効率的に線量を集中させる」という放射線治療であり、近年開発された加速器型中性子線源の登場により、将来、数多くの医療施設に普及すると期待される。加速器型BNCTでは、静脈注射によってホウ素薬剤を腫瘍部に取り込ませた後、比較的長い時間をかけて中性子線照射を行うため、照射中の腫瘍部ホウ素濃度分布が時空間的に不均一に変化する。したがって、核反応という物理学的な特性と、ホウ素薬剤の取り込みに係る薬理学・生物学的な特性が加速器型BNCTの治療効果に影響すると考えられるが、現在、このような特徴を考慮した数理モデルは開発途上にある。本稿では加速器型BNCT治療効果予測モデルの開発経緯と将来展望について概説する。, 36092723 - Hokkaido birth cohort study on environment and children's health: cohort profile 2021.
Reiko Kishi, Atsuko Ikeda-Araki, Chihiro Miyashita, Sachiko Itoh, Sumitaka Kobayashi, Yu Ait Bamai, Keiko Yamazaki, Naomi Tamura, Machiko Minatoya, Rahel Mesfin Ketema, Kritika Poudel, Ryu Miura, Hideyuki Masuda, Mariko Itoh, Takeshi Yamaguchi, Hisanori Fukunaga, Kumiko Ito, Houman Goudarzi
Environmental Health and Preventive Medicine, 26, 1, 59, 59, 2021年05月22日, [査読有り], [国際誌]
英語, 研究論文(学術雑誌), BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS: Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future. - Disaster-related Deaths in Fukushima.
Hisanori Fukunaga
Japanese Journal of Health Physics, 56, 1, 26, 27, Japan Health Physics Society, 2021年03月31日, [査読有り], [責任著者], [国内誌]
英語, 研究論文(学術雑誌) - Radiation Exposure Dose Distribution of Workers Engaged in Decontamination and Related Work Following the Fukushima Nuclear Disaster.
Hisanori Fukunaga, Tsubasa Ogawa, Tomohiro Asano, Atsuo Ito
Health Physics, 120, 3, 251, 257, Ovid Technologies (Wolters Kluwer Health), 2021年03月, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Since the Fukushima nuclear disaster in March 2011, decontamination operations have been conducted across a wide area of Japan. The Japanese System of Registration and Management of Radiation Exposure Doses for Decontamination and Related Work, which was launched in November 2013, is administered by the Radiation Effects Association with the participation of prime contractors who perform decontamination and related work. This study aims to investigate the radiation exposure dose distribution of workers engaged in decontamination and related work, using data obtained from the above registration system. We analyzed the radiation exposure dose distributions among workers in 11 Fukushima prefectural municipalities (Futaba, Iitate, Katsurao, Kawamata, Kawauchi, Namie, Naraha, Minamisōma, Okuma, Tamura, and Tomioka) from 2013 to 2018. The mean radiation exposure doses of workers in each municipality were generally low, although a Kruskal-Wallis test showed a significant regional difference in the figures. The highest mean dose was 0.5 mSv in Okuma in 2018, and the second highest was that of Futaba. The workers engaged in the land development and construction of the interim facilities may have been exposed to more radiation than other workers across 11 Fukushima prefectural municipalities. Following large-scale nuclear accidents or radiation emergencies, radiation dose monitoring and health management for each worker need to be optimized according to their work assignments. - Spatially Fractionated Microbeam Analysis of Tissue-sparing Effect for Spermatogenesis.
Hisanori Fukunaga, Kiichi Kaminaga, Takuya Sato, Karl T. Butterworth, Ritsuko Watanabe, Noriko Usami, Takehiko Ogawa, Akinari Yokoya, Kevin M. Prise
Radiation Research, 194, 6, 698, 706, Radiation Research Society, 2020年12月, [査読有り], [筆頭著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌), (Radiation Research Editors' Award 受賞論文)
Spatially fractionated radiation therapy (SFRT) has been based on the delivery of a single high-dose fraction to a large treatment area that has been divided into several smaller fields, reducing the overall toxicity and adverse effects. Complementary microbeam studies have also shown an effective tissue-sparing effect (TSE) in various tissue types and species after spatially fractionated irradiation at the microscale level; however, the underlying biological mechanism remains elusive. In the current study, using the combination of an ex vivo mouse spermatogenesis model and high-precision X-ray microbeams, we revealed the significant TSE for maintaining spermatogenesis after spatially fractionated microbeam irradiation. We used the following ratios of the irradiated to nonirradiated areas: 50:50, 150:50 and 350:50 µm-slit, where approximately 50, 75 and 87.5% of the sample was irradiated (using center-to-center distances of 100, 200 and 400 µm, respectively). We found that the 50 and 75% micro-slit irradiated testicular tissues showed an almost unadulterated TSE for spermatogenesis, whereas the 87.5% micro-slit irradiated tissues showed an incomplete TSE. This suggests that the TSE efficiency for spermatogenesis is dependent on the size of the nonirradiated spermatogonial stem cell pool in the irradiated testicular tissues. In addition, there would be a spatiotemporal limitation of stem cell migration/competition, resulting in the insufficient TSE for 87.5% micro-slit irradiated tissues. These stem cell characteristics are essential for the accurate prediction of tissue-level responses during or after SFRT, indicating the clinical potential for achieving better outcomes while preventing adverse effects. - The Effect of Low Temperatures on Environmental Radiation Damage in Living Systems: Does Hypothermia Show Promise for Space Travel?
Hisanori Fukunaga
International Journal of Molecular Sciences, 21, 17, 6349, MDPI AG, 2020年09月01日, [査読有り], [責任著者], [国際誌]
英語, 研究論文(学術雑誌), Low-temperature treatments (i.e., hypothermia) may be one way of regulating environmental radiation damage in living systems. With this in mind, hibernation under hypothermic conditions has been proposed as a useful approach for long-term human space flight. However, the underlying mechanisms of hypothermia-induced radioresistance are as yet undetermined, and the conventional risk assessment of radiation exposure during hibernation remains insufficient for estimating the effects of chronic exposure to galactic cosmic rays (GCRs). To promote scientific discussions on the application of hibernation in space travel, this literature review provides an overview of the progress to date in the interdisciplinary research field of radiation biology and hypothermia and addresses possible issues related to hypothermic treatments as countermeasures against GCRs. At present, there are concerns about the potential effects of chronic radiation exposure on neurological disorders, carcinogenesis, ischemia heat failures, and infertility in astronauts; these require further study. These concerns may be resolved by comparing and integrating data gleaned from experimental and epidemiological studies. - Alzheimer’s Disease and Specialized Pro-Resolving Lipid Mediators: Do MaR1, RvD1, and NPD1 Show Promise for Prevention and Treatment?
Keishi Miyazawa, Hisanori Fukunaga, Yasuko Tatewaki, Yumi Takano, Shuzo Yamamoto, Tatsushi Mutoh, Yasuyuki Taki
International Journal of Molecular Sciences, 21, 16, 5783, MDPI AG, 2020年08月12日, [査読有り], [責任著者], [国際誌]
英語, 研究論文(学術雑誌), Alzheimer’s disease (AD) is a common neurodegenerative disease and a major contributor to progressive cognitive impairment in an aging society. As the pathophysiology of AD involves chronic neuroinflammation, the resolution of inflammation and the group of lipid mediators that actively regulate it—i.e., specialized pro-resolving lipid mediators (SPMs)—attracted attention in recent years as therapeutic targets. This review focuses on the following three specific SPMs and summarizes their relationships to AD, as they were shown to effectively address and reduce the risk of AD-related neuroinflammation: maresin 1 (MaR1), resolvin D1 (RvD1), and neuroprotectin D1 (NPD1). These three SPMs are metabolites of docosahexaenoic acid (DHA), which is contained in fish oils and is thus easily available to the public. They are expected to become incorporated into promising avenues for preventing and treating AD in the future. - マイクロビームと組織培養を用いた放射線組織生物学 ─保健物理学と放射線生物学の接点として─
福永 久典, 横谷 明徳
保健物理, 55, 2, 92, 96, 日本保健物理学会, 2020年07月20日, [査読有り], [筆頭著者, 責任著者], [国内誌]
日本語, 研究論文(学術雑誌), (日本保健物理学会奨励賞受賞論文)
Tissue is a complex system with a highly dynamic structure to maintain a stable internal environment. The homeostatic mechanisms could be involved in radiation-induced effects at the tissue level. Also, tissue-weighting factors have been regarded as an essential index for the guideline released from the International Committee on Radiological Protection. Thus, for both radiobiology and health physics, it is important to understand radiation-induced tissue-level responses. The applications of microbeams and tissue cultures illustrated in this article focus on their relevance to radiation tissue biology that provides a novel approach for greater accuracy in risk assessment of radiation exposure. We review on recent progress in both microbeams and tissue cultures, which is promising for providing novel insights into radiation tissue biology. In addition, we present the use of ex vivo mouse testicular tissue culture as an experimental model of spermatogenesis to investigate radiobiological effects with microbeams. Our model represents a unique application in the field, with significant potential for deeper mechanistic insight into radiation-induced tissue-level effects and appropriate radiological protection. - Implications of radiation microdosimetry for accelerator-based boron neutron capture therapy: A radiobiological perspective.
Hisanori Fukunaga, Yusuke Matsuya, Koichi Tokuuye, Motoko Omura
British Journal of Radiology, 93, 20200311, British Institute of Radiology, 2020年05月06日, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Boron neutron capture therapy (BNCT) has great potential to selectively destroy cancer cells while sparing surrounding normal cells. The basic concept of BNCT was developed in the 1930s, but it has not yet been commonly used in clinical practice, even although there is now a large number of experimental and translational studies demonstrating its marked therapeutic potential. With the development of neutron accelerators that can be installed in medical institutions, accelerator-based BNCT is expected to become available at several medical institutes around the world in the near future. In this commentary, from the point of view of radiation microdosimetry, we discuss the biological effects of BNCT, especially the underlying mechanisms of compound biological effectiveness. Radiobiological perspectives provide insight into the effectiveness of BNCT in creating a synergy effect in the field of clinical oncology. - A Model for Estimating Dose-Rate Effects on Cell-Killing of Human Melanoma after Boron Neutron Capture Therapy.
Yusuke Matsuya, Hisanori Fukunaga, Motoko Omura, Hiroyuki Date
Cells, 9, 5, 1117, Multidisciplinary Digital Publishing Institute, 2020年04月30日, [査読有り], [国際誌]
英語, 研究論文(学術雑誌), Boron neutron capture therapy (BNCT) is a type of radiation therapy for eradicating tumor cells through a 10B(n,α)7Li reaction in the presence of 10B in cancer cells. When delivering a high absorbed dose to cancer cells using BNCT, both the timeline of 10B concentrations and the relative long dose-delivery time compared to photon therapy must be considered. Changes in radiosensitivity during such a long dose-delivery time can reduce the probability of tumor control; however, such changes have not yet been evaluated. Here, we propose an improved integrated microdosimetric-kinetic model that accounts for changes in microdosimetric quantities and dose rates depending on the 10B concentration and investigate the cell recovery (dose-rate effects) of melanoma during BNCT irradiation. The integrated microdosimetric-kinetic model used in this study considers both sub-lethal damage repair and changes in microdosimetric quantities during irradiation. The model, coupled with the Monte Carlo track structure simulation code of the Particle and Heavy Ion Transport code System, shows good agreement with in vitro experimental data for acute exposure to 60Co γ-rays, thermal neutrons, and BNCT with 10B concentrations of 10 ppm. This indicates that microdosimetric quantities are important parameters for predicting dose-response curves for cell survival under BNCT irradiations. Furthermore, the model estimation at the endpoint of the mean activation dose exhibits a reduced impact of cell recovery during BNCT irradiations with high linear energy transfer (LET) compared to 60Co γ-rays irradiation with low LET. Throughout this study, we discuss the advantages of BNCT for enhancing the killing of cancer cells with a reduced dose-rate dependency. If the neutron spectrum and the timelines for drug and dose delivery are provided, the present model will make it possible to predict radiosensitivity for more realistic dose-delivery schemes in BNCT irradiations. - The Tissue-Sparing Effect of Spatially Fractionated X-rays for Maintaining Spermatogenesis: A Radiobiological Approach for the Preservation of Male Fertility after Radiotherapy.
Hisanori Fukunaga, Kiichi Kaminaga, Takuya Sato, Ritsuko Watanabe, Takehiko Ogawa, Akinari Yokoya, Kevin M Prise
Journal of Clinical Medicine, 9, 4, 1089, Multidisciplinary Digital Publishing Institute, 2020年04月11日, [査読有り], [筆頭著者, 責任著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌), Radiotherapy can result in temporary or permanent gonadal toxicity in male cancer patients despite the high precision and accuracy of modern radiation treatment techniques. Previous radiobiological studies have shown an effective tissue-sparing response in various tissue types and species following exposure to spatially fractionated radiation. In the present study, we used an ex vivo mouse testicular tissue culture model and a conventional X-ray irradiation device to evaluate the tissue-sparing effect (TSE) of spatially fractionated X-rays for the protection of male fertility from radiotherapy-related adverse effects. We revealed a significant TSE for maintaining spermatogenesis in the ex vivo testes model following spatially fractionated X-ray irradiation. Moreover, we experimentally propose a possible mechanism by which the migration of spermatogonial cells, from the non-irradiated areas to the irradiated ones, in irradiated testicular tissue, is essential for the TSE and maintaining spermatogenesis. Therefore, our findings demonstrate that the control of TSE following spatially fractionated X-rays in the testes has a considerable potential for clinical application. Interdisciplinary research will be essential for further expanding the applicability of this method as an approach for the preservation of male fertility during or after radiotherapy. - High-precision microbeam radiotherapy reveals testicular tissue-sparing effects for male fertility preservation.
Hisanori Fukunaga, Kiichi Kaminaga, Takuya Sato, Karl T. Butterworth, Ritsuko Watanabe, Noriko Usami, Takehiko Ogawa, Akinari Yokoya, Kevin M. Prise
Scientific Reports, 9, 1, 12618, Springer Science and Business Media LLC, 2019年10月01日, [査読有り], [筆頭著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌), (日本放射線腫瘍学会梅垣賞受賞論文)
Microbeam radiotherapy (MRT) is based on a spatial fractionation of synchrotron X-ray microbeams at the microscale level. Although the tissue-sparing effect (TSE) in response to non-uniform radiation fields was recognized more than one century ago, the TSE of MRT in the testes and its clinical importance for preventing male fertility remain to be determined. In this study, using the combination of MRT techniques and a uniqueex vivo testes organ culture, we show, for the first time, the MRT-mediated TSE for the preservation of spermatogenesis. Furthermore, our high-precision microbeam analysis revealed that the survival and potential migration steps of the non-irradiated germ stem cells in the irradiated testes tissue would be needed for the effective TSE for spermatogenesis. Our findings indicated the distribution of dose irradiated in the testes at the microscale level is of clinical importance for delivering high doses of radiation to the tumor, while still preserving male fertility. - Updated understanding of WRN variants using the Japanese whole‐genome reference panel 3.5KJPNv2.
Hisanori Fukunaga, Kevin M Prise, Yasuyuki Taki
Geriatrics & Gerontology International, 19, 9, 961, 962, Wiley, 2019年09月, [査読有り], [筆頭著者, 責任著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌) - Diversity of ATM gene variants: a population-based genome data analysis for precision medicine.
Hisanori Fukunaga, Yasuyuki Taki, Kevin M. Prise
Human Genomics, 13, 1, 38, Springer Science and Business Media LLC, 2019年08月, [査読有り], [筆頭著者, 責任著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌), Background
Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder that causes deficiency or dysfunction of the ataxia-telangiectasia mutated (ATM) protein. Not only AT patients, but also certain ATM heterozygous mutation carriers show a significantly reduced life expectancy due to cancer and ischemic heart disease; in particular, female carriers having particular alleles have an increased risk of breast cancer. The frequency of such risk heterozygotes at a population level remains to be fully determined, and evidence-based preventive medical guidelines have not yet been established.
Methods
Using the 3.5KJPNv2 allele frequency panel of Japanese Multi Omics Reference Panel v201902, which shows single-nucleotide variant (SNV) and insertion/deletion (INDEL) allele frequencies from 3552 Japanese healthy individuals, we investigated the diversity of ATM gene variants.
Results
We detected 2845 (2370 SNV and 475 INDEL) variants in the ATM gene, including 1338 (1160 SNV and 178 INDEL) novel variants. Also, we found a stop-gained SNV (NC_000008.11:g.108115650G > A (p.Trp266*)) and a disruptive-inframe-deletion (NC_000008.11:g. 108181014AAGAAAAGTATGGATGATCAAG/A (p.Ala1945_Phe1952delinsVal) and two frameshift INDELs (NC_000008.11:g.108119714CAA/C (p.Glu376fs) and NC_000008.11:g.108203577CTTATA/C (p.Ile2629fs)), which would be novel variants predicted to lead to loss of ATM functionality.
Conclusion
The combination of population-based biobanking and human genomics provided a novel insight of diversity of ATM gene variants at a population level. For the advancement of precision medicine, such approach will be useful to predict novel pathogenic/likely pathogenic variants in the ATM gene and to establish preventive medical guidelines for certain ATM heterozygotes pertaining to their risk of particular diseases. - Precision Radiotherapy and Radiation Risk Assessment: How Do We Overcome Radiogenomic Diversity?
Hisanori Fukunaga, Akinari Yokoya, Yasuyuki Taki, Karl T. Butterworth, Kevin M. Prise
The Tohoku Journal of Experimental Medicine, 247, 4, 223, 235, Tohoku University Medical Press, 2019年04月, [査読有り], [筆頭著者, 責任著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌), Precision medicine is a rapidly developing area that aims to deliver targeted therapies based on individual patient characteristics. However, current radiation treatment is not yet personalized; consequently, there is a critical need for specific patient characteristics of both tumor and normal tissues to be fully incorporated into dose prescription. Furthermore, current risk assessment following environmental, occupational, or accidental exposures to radiation is based on population effects, and does not account for individual diversity underpinning radiosensitivity. The lack of personalized approaches in both radiotherapy and radiation risk assessment resulted in the current situation where a population-based model, effective dose, is being used. In this review article, to stimulate scientific discussion for precision medicine in both radiotherapy and radiation risk assessment, we propose a novel radiological concept and metric – the personalized dose and the personalized risk index – that incorporate individual physiological, lifestyle-related and genomic variations and radiosensitivity, outlining the potential clinical application for precision medicine. We also review on recent progress in both genomics and biobanking research, which is promising for providing novel insights into individual radiosensitivity, and for creating a novel conceptual framework of precision radiotherapy and radiation risk assessment. - Personalised Risk Assessment of Low-dose Radiation Effects on Spermatogenesis.
Hisanori Fukunaga
Queen's University Belfast Doctoral Thesis, Queen's University Belfast, 2019年
英語, 学位論文(博士), *Thesis for the degree of Doctor of Philosophy submitted to the School of Medicine, Dentistry, and Biomedical Sciences. - Non-uniform radiation-induced biological responses at the tissue level involved in the health risk of environmental radiation: a radiobiological hypothesis.
Hisanori Fukunaga, Kevin M. Prise
Environmental Health, 17, 1, 93, Springer Science and Business Media LLC, 2018年12月, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌), Background: The conventional concept of radiation protection is based on epidemiological studies of radiation that support a positive correlation between dose and response. However, there is a remarkable difference in biological responses at the tissue level, depending on whether radiation is delivered as a uniform or non-uniform spatiotemporal distribution due to tissue sparing effects (TSE). From the point of view of radiation micro-dosimetry, environmental radiation is delivered as a non-uniform distribution, and radiation-induced biological responses at the tissue level, such as TSE, would be implicated in individual risk following exposure to environmental radiation.
Hypothesis: We hypothesize that the health risks of non-uniform radiation exposure are lower than the same dose at a uniform exposure, due to TSE following irradiation. Testing the hypothesis requires both radiobiological studies using high-precision microbeams and the epidemiological data of environmental radiation-induced effects. The implications of the hypothesis will lead to more personalized approaches in the field of environmental radiation protection.
Conclusion: The detection of spatiotemporal dose distribution could be of scientific importance for more accurate individual risk assessment of exposure to environmental radiation. Further radiobiological studies on non-uniform radiation-induced biological responses at the tissue level are expected. - Microbeam evolution: from single cell irradiation to pre-clinical studies
Mihaela Ghita, Cristian Fernandez-Palomo, Hisanori Fukunaga, Pil M. Fredericia, Giuseppe Schettino, Elke Bräuer-Krisch, Karl T. Butterworth, Stephen J. McMahon, Kevin M. Prise
International Journal of Radiation Biology, 94, 8, 708, 718, Informa UK Limited, 2018年07月28日, [査読有り], [招待有り], [国際共著], [国際誌]
英語, 研究論文(学術雑誌) - Application of an Ex Vivo Tissue Model to Investigate Radiobiological Effects on Spermatogenesis
Hisanori Fukunaga, Kiichi Kaminaga, Takuya Sato, Noriko Usami, Ritsuko Watanabe, Karl T. Butterworth, Takehiko Ogawa, Akinari Yokoya, Kevin M. Prise
Radiation Research, 189, 6, 661, 667, Radiation Research Society, 2018年06月, [査読有り], [筆頭著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌) - A case of low-grade primary cardiac lymphoma with pericardial effusion diagnosed by combined18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) imaging and effusion cytology
Hisanori Fukunaga, Yasuko Tatewaki, Tatsushi Mutoh, Hideo Shimomura, Shuzo Yamamoto, Chiaki Terao, Tomoko Totsune, Manabu Nakagawa, Yasuyuki Taki
American Journal of Case Reports, 19, 292, 295, International Scientific Information, Inc., 2018年03月14日, [査読有り], [筆頭著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌) - Low-dose radiation-induced risk in spermatogenesis
Hisanori Fukunaga, Karl T. Butterworth, Akinari Yokoya, Takehiko Ogawa, Kevin M. Prise
International Journal of Radiation Biology, 93, 12, 1291, 1298, 2017年12月02日, [査読有り], [筆頭著者, 責任著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌) - Neuro-myelomatosis of the brachial plexus – An unusual site of disease visualized by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT): A case report
Hisanori Fukunaga, Tatsushi Mutoh, Yasuko Tatewaki, Hideo Shimomura, Tomoko Totsune, Chiaki Terao, Hidemitsu Miyazawa, Yasuyuki Taki
American Journal of Case Reports, 18, 478, 481, International Scientific Information, Inc., 2017年05月01日, [査読有り], [筆頭著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌) - An autopsy of intravascular large B-cell lymphoma with hemophagocytic syndrome
Hisanori Fukunaga, Kazumasa Kawashima, Hiromi Kumakawa, Yuko Hashimoto, Yuta Takahashi
JRSM Open, 8, 5, 205427041769505, 205427041769505, SAGE Publications, 2017年05月, [査読有り], [筆頭著者]
英語, 研究論文(学術雑誌), Intravascular large B-cell lymphoma presents with highly variable symptoms caused by the occlusion of small vessels by neoplastic cells in a variety of organs. - Radiobiological Implications of Fukushima Nuclear Accident for Personalized Medical Approach
Fukunaga Hisanori, Yokoya Akinari, Taki Yasuyuki, Prise Kevin M.
The Tohoku Journal of Experimental Medicine, 242, 1, 77, 81, 2017年05月, [査読有り], [筆頭著者, 責任著者], [国際共著], [国際誌]
英語, 研究論文(学術雑誌) - Collision tumor with diffuse large B cell lymphoma and gastric cancer.
Fukunaga H, Asama H, Kaneda H, Takahashi Y
Japanese Journal of Clinical Oncology, 46, 10, 968, 969, 2016年10月, [査読有り], [筆頭著者], [国際誌]
英語, 研究論文(学術雑誌) - Now Is the Time to Consider Personalized Effective Dose.
Fukunaga H, Yokoya A, Taki Y
International Journal of Radiation Oncology, Biology, Physics, 96, 2, 479, 480, 2016年10月, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌) - Unsung Heroes Throughout the 2011 Fukushima Catastrophe.
Fukunaga H, Sato M
Family Medicine, 48, 6, 482, 483, 2016年06月, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌) - Clinical examinations after the Fukushima disaster: a case report of Soma General Hospital.
Fukunaga H, Hoshi Y, Takahashi Y
Clinical Chemistry and Laboratory Medicine, 54, 4, e133, e134, 2016年04月, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌) - Asymptomatic Primary Malignant Melanoma of the Gastroesophageal Junction.
Fukunaga H, Kaneda H, Kumakawa H, Takahashi Y
Internal Medicine, 55, 6, 709, 710, 2016年03月, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌) - Hemodialysis after the Fukushima disaster: a case report of Soma General Hospital.
Fukunaga H, Manome M
Clinical and Experimental Nephrology, 20, 1, 151, 152, 2016年02月, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌) - Low-dose radiation risk and individual variation in radiation sensitivity in Fukushima.
Fukunaga H, Yokoya A
Journal of Radiation Research, 57, 1, 98, 100, 2016年01月, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌) - 患者数と処方箋数の変遷から見た東日本大震災直後の被災地医療:公立相馬総合病院ケースレポート
福永 久典, 桃井 俊幸, 熊川 宏美
薬学雑誌, 136, 1, 139, 142, 2016年01月, [査読有り], [筆頭著者, 責任著者], [国内誌]
日本語, 研究論文(学術雑誌) - Mental Health Crisis in Northeast Fukushima after the 2011 Earthquake, Tsunami and Nuclear Disaster
Hisanori Fukunaga, Hiromi Kumakawa
The Tohoku Journal of Experimental Medicine, 237, 1, 41, 43, 2015年09月, [査読有り], [筆頭著者, 責任著者]
英語, 研究論文(学術雑誌) - Radiology After the Fukushima Disaster: A Case Report Of Soma General Hospital
Hisanori Fukunaga, Shigeyoshi Owada
Journal of the American College of Radiology, 12, 8, 773, 774, 2015年08月, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌) - After the earthquake, tsunami and nuclear crisis
Hisanori Fukunaga
Journal of the Royal Society of Medicine, 108, 4, 151, 152, 2015年04月, [査読有り], [責任著者], [国際誌]
英語, 研究論文(学術雑誌) - Disaster Management at Soma General Hospital in Response to the Great East Japan Earthquake.
Fukunaga H, Kumakawa H
Japan Medical Association Journal : JMAJ, 57, 5-6, 331, 334, 2014年12月, [査読有り], [招待有り], [筆頭著者, 責任著者], [国内誌]
英語, 研究論文(学術雑誌) - Relative age effect on Nobel laureates in the UK.
Fukunaga H, Taguri M, Morita S
JRSM Short Reports, 4, 10, 2042533313492514, 204253331349251, {SAGE} Publications, 2013年, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌) - Label-free biomedical imaging of hydrodynamics in single human cells.
Fukunaga H, Yoshimura H, Nishina Y, Nagashima Y, Tachibana M
Biomedical Research, 31, 3, 177, 181, 2010年, [査読有り], [筆頭著者, 責任著者], [国際誌]
英語, 研究論文(学術雑誌)
その他活動・業績
- ミトコンドリアゲノム制御に関する放射線の次世代影響
福永 久典, Isotope News, 802, 2, 5, 2025年12月, [招待有り], [責任著者], [国内誌]
日本アイソトープ協会, 日本語, 記事・総説・解説・論説等(大学・研究所紀要) - ストライプ状照射を用いた精子形成能維持と臨床応用
福永 久典, 横谷 明徳, Isotope News, 771, 24, 27, 2020年10月, [招待有り], [筆頭著者], [国内誌]
日本アイソトープ協会, 日本語, 記事・総説・解説・論説等(大学・研究所紀要) - 不均一な放射線被ばく後の精子形成能の検討 ~原子力災害後の環境放射線被ばくリスクの解明を目指して~
福永 久典, 第33回独創性を拓く先端技術大賞 フジテレビジョン賞, 2019年07月, [責任著者]
*第33回(2019年度)独創性を拓く先端技術大賞・フジテレビジョン賞受賞論文, フジサンケイ ビジネスアイ, 日本語, 記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
書籍等出版物
- 〔主要な業績〕外部放射線被ばくに対する実用量(ICRU Report 95 邦訳版)
甲斐 倫明, 鈴木 元, 佐々木 道也, 大野 和子, 小田 啓二, 川口 勇生, 木内 伸幸, 迫田 幸子, 佐々木 康人, 谷村 嘉彦, 半谷 英樹, 福永 久典, 保田 浩志, ICRP刊行物翻訳委員会
原子力規制委員会, 2026年03月, 160, 日本語, 調査報告書, *ICRU Report 95 Operational Quantities for External Radiation Exposure の邦訳, [共編者(共編著者)] - 〔主要な業績〕放射線防護における線量の使用(ICRP Publication 147 邦訳版)
甲斐 倫明, 鈴木 元, 佐々木 道也, 大野 和子, 小田 啓二, 川口 勇生, 木内 伸幸, 迫田 幸子, 佐々木 康人, 谷村 嘉彦, 半谷 英樹, 福永 久典, 保田 浩志, ICRP刊行物翻訳委員会
原子力規制委員会, 2026年02月, 88, 日本語, 調査報告書, *ICRP Publication 147 Use of Dose Quantities in Radiological Protection の邦訳, [共編者(共編著者)] - Never Let the Light Fade: Memories of Soma General Hospital in Fukushima
Hisanori Fukunaga
Amazon Kindle, 2018年08月, 129, 英語, 一般書・啓蒙書, *英語・電子書籍(ASIN: B07G7XXJ1T)
*金原一郎記念医学医療振興財団研究出版助成, [単著]
産業財産権
メディア報道
- Preconception Radiation Exposure Causes Organ-Specific Changes in Offspring Mitochondrial DNA
2026年04月17日
本人以外
Bioengineer.org
35821660, [インターネットメディア] - Preconception radiation exposure alters offspring mitochondrial DNA in an organ-specific manner
2026年04月17日
本人以外
American Association for the Advancement of Science (AAAS)
EurekAlert!
35821660, [インターネットメディア] - A 'Glowing Sperm' Mouse Model Enables Real-Time Tracking of Infertility and Recovery
2026年03月11日
本人以外
Japan Science and Technology Agency (JST)
Science Japan
35821660, [インターネットメディア] - A smarter approach to testing reproductive safety
2026年03月10日
本人以外
American Association for the Advancement of Science (AAAS)
EurekAlert!
35821660, [インターネットメディア]
その他
- 2026年04月
Preconception radiation exposure alters offspring mitochondrial DNA in an organ-specific manner
*Release from the Hokkaido University - 2026年03月
A smarter approach to testing reproductive safety
*Release from the Hokkaido University - 2025年10月
Hisanori Fukunaga to Receive John D. Boice, Jr. Young Investigator Award
*Release from the National Council on Radiation Protection and Measurements (USA) - 2019年10月
「ストライプ照射」だと放射線の影響は軽減される ~放射線の当たり方が一様でない場合、従来の単純な予測は当てはまらない~
*量子科学技術研究開発機構、Queen's University Belfast、横浜市立大学、高エネルギー加速器研究開発機構から研究成果プレスリリース
