Model development for estimating radiation effects in non-uniform radiation fields

• Project/Area Number: 19K17215
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Japan Atomic Energy Agency
• Principal Investigator: Matsuya Yusuke 国立研究開発法人日本原子力研究開発機構, 原子力科学研究部門 原子力科学研究所 原子力基礎工学研究センター, 研究員 (20826929)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 不均一照射 / 細胞死 / 細胞間シグナリング / 数理モデル / DNA損傷 / 酸素効果 / 細胞間シグナル効果 / 活性酸素種 / 細胞生存率 / DNA損傷生成率 / 照射中のDNA修復 / 数理モデル開発 / DNA二本鎖切断 / DNA修復

Outline of Research at the Start

電離放射線照射時の細胞応答として，非照射細胞が照射細胞と同様の生物学的効果を示す細胞間シグナリングが近年注目されている。一方で，非照射細胞から照射細胞へのシグナル伝達によって誘発する放射線抵抗性（防御効果）も近年報告されているが，照射細胞と非照射細胞間の双方向のシグナル効果が放射線感受性へ与える影響に対する研究は不十分である。そこで本研究では，細胞実験とモデル研究を組合せた研究により，双方向の細胞間シグナルのメカニズム解明を試みる。本研究が完遂すれば，放射線防護や強度変調放射線治療（分割照射）時のより正確な正常組織へのダメージと治療効果を評価が可能となる。

Outline of Final Research Achievements

In this study, we investigated the biological effects by intercellular signaling between irradiated and non-irradiated cells under non-uniform radiation fields from standpoints of cell experiments and computational science. Modifying an existing cell-killing model, we have developed a new model considering intercellular signaling between irradiated and non-irradiated cells. Using simple non-uniform radiation field, in which 50% area of cell culture flask was shielded, and complex clinical radiation fields, we also evaluated the impact of intercellular signaling on radiosensitivity. Through these studies, we have succeeded in developing a theoretical model that enables predicting tumor control and side effects of normal cells in intensity-modulated radiation therapy with high precision.

Academic Significance and Societal Importance of the Research Achievements

染色体スケールの微視的エネルギー付与分布やDNA損傷応答、細胞間シグナリングを総合的に考慮して、不均一放射線照射後に発生する細胞死を再現する数理モデルの開発に成功した。様々な不均一放射線場にて変化する放射線感受性を高精度に予測可能な本研究のモデリングは、効率的な腫瘍制御法や正常細胞の副反応の評価を実現する基盤となるものである。今後本研究で得られた成果を基盤に研究を進展させることにより、放射線被ばく後の生物学的効果の正確な理解につながると考えられる。

Research Products

• [Int'l Joint Research] クイーンズ大学ベルファスト(英国)
• [Int'l Joint Research] クイーンズ大学ベルファスト(英国)
• [Journal Article] Tumor radioresistance caused by radiation-induced changes of stem-like cell content and sub-lethal damage repair capability (2022)
  • Author(s): Fukui Roman、Saga Ryo、Matsuya Yusuke、Tomita Kazuo、Kuwahara Yoshikazu、Ohuchi Kentaro、Sato Tomoaki、Okumura Kazuhiko、Date Hiroyuki、Fukumoto Manabu、Hosokawa Yoichiro
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 1056-1056
  • DOI: 10.1038/s41598-022-05172-4
  • Peer Reviewed / Open Access
• [Journal Article] Oxygen enhancement ratios of cancer cells after exposure to intensity modulated x-ray fields: DNA damage and cell survival (2021)
  • Author(s): Matsuya Yusuke、McMahon Stephen J、Butterworth Karl T、Naijo Shingo、Nara Isshi、Yachi Yoshie、Saga Ryo、Ishikawa Masayori、Sato Tatsuhiko、Date Hiroyuki、Prise Kevin M
  • Journal Title: Physics in Medicine & Biology Volume: 66 Issue: 7 Pages: 075014-075014
  • DOI: 10.1088/1361-6560/abf011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Model for Estimating Dose-Rate Effects on Cell-Killing of Human Melanoma after Boron Neutron Capture Therapy (2020)
  • Author(s): Matsuya Yusuke、Fukunaga Hisanori、Omura Motoko、Date Hiroyuki
  • Journal Title: Cells Volume: 9 Issue: 5 Pages: 1117-1117
  • DOI: 10.3390/cells9051117
  • Peer Reviewed / Open Access
• [Journal Article] A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields (2020)
  • Author(s): Matsuya, Y., Nakano, T., Kai, T., Shikazono, N., Akamatsu, K., Yoshii, Y, Sato, T.
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 5 Pages: 1-13
  • DOI: 10.3390/ijms21051701
  • Peer Reviewed / Open Access
• [Journal Article] A theoretical cell-killing model to evaluate oxygen enhancement ratios at DNA damage and cell survival endpoints in radiation therapy (2020)
  • Author(s): Y. Matsuya, T. Sato, R. Nakamura, S. Naijo, H. Date
  • Journal Title: Physics in Medicine and Biology Volume: 65(9), 095006 Issue: 9 Pages: 1-12
  • DOI: 10.1088/1361-6560/ab7d14
  • NAID: 120007029081
  • Peer Reviewed
• [Journal Article] Intensity Modulated Radiation Fields Induce Protective Effects and Reduce Importance of Dose-Rate Effects (2019)
  • Author(s): Y. Matsuya, S. J. McMahon, M. Ghita, Y. Yoshii, T. Sato, H. Date, K. M. Prise
  • Journal Title: Scientific Reports Volume: 9,9483 Issue: 1 Pages: 1-12
  • DOI: 10.1038/s41598-019-45960-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Modeling of yield estimation for DNA strand breaks based on Monte Carlo simulations of electron track structure in liquid water (2019)
  • Author(s): Y. Matsuya, T. Kai, Y. Yoshii, Y. Yachi, S. Naijo, H. Date, T. Sato
  • Journal Title: Journal of Applied Physics Volume: 126, 124701 Issue: 1 Pages: 1-8
  • DOI: 10.1038/s41598-019-54081-6
  • NAID: 120006887722
  • Peer Reviewed
• [Presentation] An integrated theoretical model for estimating cell death based on the DNA damage response (2021)
  • Author(s): Y. Matsuya, S.J. McMahon, T. Sato, K.T. Butterworth, R. Saga, H. Date, K.M. Prise
  • Organizer: 日本放射線影響学会第64回大会
  • Invited
• [Presentation] 中性子照射中の細胞内ホウ素濃度とDNA修復効果を考慮したBNCT治療効果予測モデルの開発 (2021)
  • Author(s): 松谷悠佑，大村素子，福永久典
  • Organizer: 日本放射線腫瘍学会第34回学術大会
• [Presentation] Protective effects induced following the exposure to modulated radiation intensity reduce importance of dose-rate effects (2019)
  • Author(s): Y. Matsuya, S.J. McMahon, M. Ghita, T. Sato, Y. Yoshii, T. Kai, H. Date, K.M. Prise
  • Organizer: 日本放射線影響学会第62回大会