2018 Fiscal Year Final Research Report
Studies on defensive cellular response by nucleus and cytoplasm targeted irradiation using microbeam
| Project/Area Number |
16K15586
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Radiation science
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| Research Institution | National Institutes for Quantum and Radiological Science and Technology |
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Principal Investigator |
Konishi Teruaki 国立研究開発法人量子科学技術研究開発機構, 放射線障害治療研究部, 主任研究員(定常) (70443067)
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| Research Collaborator |
KOBAYASHI Alisa
OHSAWA Daisuke
OIKAWA Masakazu
FURUSAWA Yoshiya
WANG Jun
AUTSAVAPROMPORN Narongchai
Tengku Ahmad Tengku Ahbrizal Farizal
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | マイクロビーム / 細胞質 / ミトコンドリア / 酸化ストレス応答 / NRF2 / DNA修復 / Mito-Sox |
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| Outline of Final Research Achievements |
Our aim was to clarify the radiation induced cytoplasmic damage and its cellular response. Taking advantage of the advanced technology of SPICE-NIRS microbeam, we were able to precisely target the nucleus and cytoplasm. Experimentally, human lung normal cells were microbeam targeted in the nucleus, cytoplasm, or both to investigate the site-specific cellular response. As result, cytoplasmic irradiation induced DNA double strand breaks as a result of cellular response of mitochondria damage and not because of direct energy deposition by the proton beam. In addition, we found that activation of NRF2, a transcriptional factor of anti-oxidative response gene, and upregulation of responsible target genes. Altogether, we demonstrated that cytoplasmic damage triggers defensive cellular response against radiation, that were followed by activation oxidative response pathway and also DSB repair pathway.
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| Free Research Field |
放射線生物学
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| Academic Significance and Societal Importance of the Research Achievements |
本課題では、放射線によって誘発される細胞質損傷を起因とする細胞応答は、DNA損傷の修復過程を促進するという結果を報告した。放射線による生物効果の第一ターゲットはDNAであるとした古典的な放射線生物学に対して、本研究では、第二ターゲットとして細胞質が存在し、それは放射線に対して防御的に働くことを示したことは学術的に重要であり、放射線以外の基礎生物学分野においても発展性が大きいと考える。そして、細胞の放射線感受性を左右するであろう細胞質損傷応答およびその経路は、放射線リスク推定とモデル化、並びに放射線がん治療においても、重要なファクターになり得ることからその社会的な意義は大きいと考える。
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