Radiobiological study on hypofractionated high-precision radiotherapy

• Project/Area Number: 26461887
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Osaka University
• Principal Investigator: Seo Yuji 大阪大学, 医学系研究科, 助教 (00302000)
• Co-Investigator(Kenkyū-buntansha): 小川 和彦 大阪大学, 医学系研究科, 教授 (40253984)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 高精度放射線治療 / DNA2本鎖切断修復 / 相同組換え修復 / 非相同末端接合 / 放射線 / 癌 / 定位放射線治療 / 放射線治療学 / 放射線増感剤 / LQモデル

Outline of Final Research Achievements

We investigated cellular responses to a high-dose-per-fraction radiotherapy compared with a conventionally fractionated radiotherapy. Based on an analysis using biomathematical models, underlying mechanisms of radiosensitizing effects were classified into three factors: 1) Increase of initial DNA damages, 2) Inhibition of DNA double-strand break (DNA-DSB) repairs, and 3) Increased chromosomal translocations mediated by non-homologous end joining. Since a probability of chromosomal translocations is proportional to a square dose, the third mechanism enhanced radiosensitivity in the high dose range to a greater extent than the second mechanism. Through the third mechanism, the altered selection of DNA-DSB repair pathways impacted on radiosensitivity without any changes in the total amount of the initial DNA damage and its repair. The pathway choice of the DNA-DSB repair can be a potential molecular target for hypofractionated high-precision radiotherapy.

Research Products

• [Journal Article] Characterization of in vitro radiosensitization in mammalian cells using biomathematical modelling: implications for hypofractionated radiotherapy with a combined modality approach (2016)
  • Author(s): Seo, Y., Tamari, K., Yoshioka, Y., Isohashi, F., Suzuki, O., Hayashi, K.,Takahashi, Y., Baek, S., Otani, K., Ogawa, K.
  • Journal Title: The British Journal of Radiology Volume: 89 Issue: 1062 Pages: 20150724-20150724
  • DOI: 10.1259/bjr.20150724
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Poly(ADP-ribose) polymerase inhibitors induce β-radiosensitization through an altered selection of DNA double-strand break repair pathways (2017)
  • Author(s): Yuji Seo
  • Organizer: Annual meeting of the American Association for Cancer Research
  • Place of Presentation: Washington, DC (USA)
  • Year and Date: 2017-04-01
  • Int'l Joint Research
• [Presentation] Systematic Linear-Quadratic Analysis for Radiosensitization in vitro: Implications for Hypofractionated (2014)
  • Author(s): Y. Seo, K. Yoshizaki, K. Hayashi, K. Tamari, F. Isohashi, O. Suzuki, Y. Yoshioka, K. Ogawa
  • Organizer: 56th Annual meeting of the American Society of Radiation Oncology
  • Place of Presentation: 米国・サンフランシスコ
  • Year and Date: 2014-09-14 – 2014-09-17