Effect of alpha-emitting seed on cell cycle kinetics of oral cancer cells and development of radiosensitizing methods

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K23046
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Nojima Hitomi 東京医科歯科大学, 東京医科歯科大学病院, 特任助教 (40878203)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: α線源 / 小線源治療 / 口腔がん / 細胞周期 / 放射線増感法

Outline of Final Research Achievements

Using several cell lines expressing Fucci, I detected strong G2 arrest near the alpha seed in a time dependent manner. Cells were released from G2 arrest and cell death increased following the WEE1 inhibitor treatment, which is able to inhibit radiation-induced G2 arrest. In the mouse model, it was also found that a remarkable G2 arrest was induced near the seed. DNA damage was detected by the expression of γH2AX. It decreased in a distance dependent manner from the seed, and a unrepairable and fatal pan-nuclear type was detected near the seed. In this study, for the first time, I could reveal the kinetics of DNA damage response near the alpha-emitting Ra-224 seed using human tongue cancer cell lines and suggest a possible radiosensitization by G2/M checkpoint inhibitor.

Free Research Field

放射線生物学、放射線腫瘍学

Academic Significance and Societal Importance of the Research Achievements

口腔がんに対する低線量率小線源治療は有用であるが、従来治療に用いてきたγ線源は、抵抗性を示すがんの存在や術者の被曝等が問題であった。これらの問題点を解決することが期待できるα線を利用した治療法が近年開発され、従来の局所腫瘍内照射の利点とα線の破壊力を有する画期的な治療法といえる。しかし、新しい治療法であるが故に放射線生物学的知見はほとんど得られていない。また、これまで放射線治療と併用することで増感作用を示す様々な薬剤が開発されてきたが、未だ臨床応用に至っていない。α線による細胞動態を把握することでより良い治療法を開発するとともに、薬剤により増感させることが可能になれば臨床応用につながる。