Visualization of cluster damage in cells and tumors and elucidation of repair mechanisms

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K12248
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 63020:Radiation influence-related
• Research Institution: National Institutes for Quantum Science and Technology
• Principal Investigator: Toshiaki Nakano 国立研究開発法人量子科学技術研究開発機構, 量子生命科学研究所, 主幹研究員 (10526122)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: DNA損傷 / cluster DNA damage / irradiation

Outline of Final Research Achievements

Radiation-induced localized multiple damage sites in DNA, known as clustered DNA damage, are believed to be closely related to the biological effects of radiation. However, there has been no established method for analyzing clustered damage until now. In response, we developed a technique to label DNA damage sites, making them visible at a size detectable by atomic force microscopy (AFM). This advancement allows for the analysis of these sites using AFM. By applying this method, we were able to measure the production and repair rates of various types of DNA damage in the genomic DNA extracted from irradiated TK6 cells. Consequently, we successfully elucidated the repair mechanisms for individual types of DNA damage.

Free Research Field

放射線生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、鎖切断を伴わないクラスターDNA損傷（シンプルクラスター損傷や高密度クラスター損傷）は効率的に修復される一方で、DSBを伴う高複雑度DSB（DSB＋塩基）は特に高LETの鉄イオン照射後に長期間生体内に存在し続けることを明らかにした。これにより、クラスターDNA損傷の定量と修復効率の評価が可能となり、電離放射線の生物学的影響を理解する上で極めて重要な知見が得られた。本研究は、放射線治療や化学療法による腫瘍治療、および正常細胞の発がんリスクに関連するクラスター損傷の生物学的影響を評価する上で重要な進展をもたらすと考えられる。