Elucidation of TRPM2-mediated pathogenesis of radiation-induced myelosuppression

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15644
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Teikyo Heisei University
• Principal Investigator: ISHIBASHI MASAAKI 帝京平成大学, 薬学部, 助教 (80771534)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: TRPM2 / 放射線 / 骨髄抑制 / マウス / ドキソルビシン

Outline of Final Research Achievements

The aim of this study was to clarify the relationship between TRPM2, which is known to induce cell death, and the development of radiation-induced myelosuppression. However, the reduction of CFU-GM colony numbers caused by irradiation were not different between wild-type (WT) and TRPM2 knockout (TRPM2KO) mice. These results were suggesting that TRPM2 was may not contribute to radiation-induced bone marrow toxicity. The association between doxorubicin (DXR)-induced myelotoxicity and TRPM2 were also studied. The reduction of CFU-GM colony numbers caused by DXR administration were not different WT and TRPM2KO mice. We were unable to indicate an association between radiation or DXR-induced myelosuppression and TRPM2.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

がん治療における抗がん剤、放射線による骨髄抑制は、重要な有害事象である。そのため、詳細な発症機構を明らかにすることで、がん治療における有害事象の軽減を実現することに繋がると考えられる。本研究では、放射線・DXRによる骨髄抑制の発現とTRPM2の関連性が低いとの結論に至った。しかし、検討の過程でDXRが過酸化水素によるTRPM2の活性化を増強させる可能性を見出した。DXRによる有害事象には、心筋症、血管外漏出、手足症候群などが挙げられる。本研究の結果は、DXRの有害事象の発症機構におけるTRPM2の関連を解明するために有用であると考えられる。