Elucidation of radiation-induced mammary carcinogenic mechanism by capturing spatiotemporal dynamics of mammary stem cells

• Project/Area Number: 18K11652
• 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 and Radiological Science and Technology
• Principal Investigator: IIZUKA Daisuke 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線影響研究部, 研究統括(定常) (00455388)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 放射線発がん / 乳腺 / 幹細胞 / 三次元免疫組織学的解析 / 細胞系譜追跡 / 乳腺幹細胞 / 細胞系譜トレーシング解析 / 組織透明化 / 放射線被ばく

Outline of Final Research Achievements

Carcinogenic risk from low-dose radiation exposure is an important issue that must be scientifically clarified, and stem cells are considered to be the origin of radiation carcinogenesis. Therefore, in this study, we set up a cell lineage tracing experiment that can trace stem cells and their progenies and a three-dimensional immunohistochemical analysis in combination with tissue clearing. Using these techniques, we observed relatively early cell dynamics after radiation exposure. We could evaluate the presence of labeled stem cells and whether they were proliferating or not. This suggests the possibility of observing the effects of radiation exposure on mammary stem cells.

Academic Significance and Societal Importance of the Research Achievements

本研究では放射線誘発乳がんメカニズムを明らかにするために、放射線発がんの起源細胞と考えられる幹細胞に着目し、解析するための技術を導入した。これにより、放射線被ばくしてがんに至る幹細胞の動態を動物実験で明らかにすることが可能となった。将来的には福島原発事故で露呈した、100 mGy以下の被ばくによる発がんリスクを科学的に明らかにすることができると考えられる。

Research Products

• [Presentation] Elucidating the mechanism of radiation-induced mammary carcinogenesis by tracing stem cell dynamics. (2020)
  • Author(s): Daisuke Iizuka, Chizuru Tsuruoka, Tatsuhiko Imaoka, Shizuko Kakinuma
  • Organizer: 第79回日本癌学会学術総会
• [Presentation] 将来的な量子センサー計測の可能性を志向した幹細胞系譜追跡実験系を用いた放射線発がんメカニズム解明 (2020)
  • Author(s): 飯塚 大輔, 鶴岡 千鶴, 品川 まゆみ, 砂押 正章, 今岡 達彦, 柿沼 志津子
  • Organizer: 量子生命科学会第2回大会
• [Presentation] Evaluation of low-dose radiation effect on tissue stem cells using three-dimensional histology method. (2019)
  • Author(s): Daisuke Iizuka, Chiuru Tsuruoka, Masaaki Sunaoshi, Mayumi Shinagawa, Tatsuhiko Imaoka, Shizuko Kakinuma.
  • Organizer: 日本放射線影響学会第62回大会
• [Presentation] Establishment of three-dimensional histological analysis method for elucidating tissue dynamics after low-dose radiation exposure. (2019)
  • Author(s): Daisuke Iizuka, Chizuru Tsuruoka, Masaaki Sunaoshi, Mayumi Shinagawa, Tatsuhiko Imaoka, Shizuko Kakinuma.
  • Organizer: 65th Annual International Meeting Radiation Research Society
  • Int'l Joint Research
• [Presentation] Evaluation of low-dose radiation effect on mammary stem cells using three-dimensional immunnohistochemical analysis. (2018)
  • Author(s): Daisuke Iizuka, Tatsuhiko Imaoka, Yukiko Nishimura, Shizuko Kakinuma.
  • Organizer: 第16回幹細胞シンポジウム