2019 Fiscal Year Final Research Report

The influence of superhypofractionated irradiation with long interfraction intervals and adaptive responses and clinical application in the latest proton beam technology

Research Project

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Project/Area Number	16K10400
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Radiation science
Research Institution	Nagoya City University
Principal Investigator	Sugie Chikao 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (80509258)
Co-Investigator(Kenkyū-buntansha)	岩田宏満名古屋市立大学, 医薬学総合研究院(医学), 研究員 (40611588) 荻野浩幸名古屋市立大学, 医薬学総合研究院(医学), 高度医療教育研究センター教授 (60315885)
Project Period (FY)	2016-04-01 – 2020-03-31
Keywords	亜致死損傷の回復（SLDR） / 潜在致死損傷の回復（PLDR） / 直接作用 / 低線量率長時間放射線被曝 / Hsp90阻害薬 / DNA二本鎖切断（DNA DSB） / 適応応答 / 放射線ホルミシス
Outline of Final Research Achievements	Compared with that seen after X-ray irradiation, Sublethal damage recovery (SLDR) might take place to a lesser extent after proton beam irradiation. The extent of potentially lethal damage recovery (PLDR) does not differ between these two conditions. The contribution of the direct effect in proton beam irradiation seemed to be greater than that in X-rays. In vivo, hormetic effects by continuous low-dose irradiation were demonstrated using low-dose-radiation-emitting sheets. These effects included promotion of growth and an increase in the time to tumor development. In vitro, the adaptive response by continuous low-dose radiation was demonstrated. One reason for the adaptive response may be efficient DNA double-strand break (DSB) repair. Anti-tumor effects of a Hsp90 inhibitor was observed in combination with both X-ray irradiation and proton beam irradiation. The mechanism behind this effect is likely to relate to the observed downregulation of DNA DSB repair.
Free Research Field	放射線医学分野
Academic Significance and Societal Importance of the Research Achievements	陽子線照射後のSLDRはX線に比し抑制されていること、陽子線の直接作用の割合がX線より高いことを明らかにすることで、陽子線治療が放射線生物学的効果に優れるということを立証した。低線量率長時間放射線被曝の生体内および細胞レベルでの影響を明らかにし、その放射線生物学的機序につき一定の知見を得た。また、Hsp90阻害薬による陽子線照射の増感効果とその機序につき明らかにしつつある。以上の研究成果は、最新技術を用いた陽子線治療の最適な治療指針の確立とその効果の増強という目的に向けて有意義なものと考えられる。