Analysis of the function of the senescent cells for exploring the link between ionizing radiation and carcinogenesis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K12322
• 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: Hiroshima University
• Principal Investigator: Kawai Hidehiko 広島大学, 医系科学研究科(薬), 准教授 (30379846)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 放射線 / 発がん / 幹細胞 / 変異 / 微小環境

Outline of Final Research Achievements

To elucidate the mechanism of radiation carcinogenesis, we analyzed the radiation-induced cellular responses and mutations of irradiated iPS cells or iPS cells co-cultured with fibroblasts in which cellular senescence was induced by radiation, in order to investigate stem cell-specific mutations induced by radiation exposure. The results revealed that the mutations occurring in iPS cells were mediated by a certain DNA replication mechanism. Although stem cells were much less prone to radiation-induced mutations, such mutations were increased by cellular microenvironment, p53-status, and other many factors. The results of this study provide a new insight into the mechanism for radiation carcinogenesis.

Free Research Field

放射線影響

Academic Significance and Societal Importance of the Research Achievements

放射線被曝によるがんでは、被曝の爪痕としての特異的な変異が検出されず、その発がんプロセスは未解明である。本研究では、放射線によって幹細胞特異的に誘発される細胞応答性と変異に注目し、解析を行った。その結果、幹細胞におけるp53の機能、および、放射線により細胞老化が誘導された間質系細胞の幹細胞への影響、の2つの観点から、放射線によって幹細胞に誘発される変異に関し、新たな知見を得た。放射線によって幹細胞特異的に誘発される変異とその誘発機構の解明は、放射線発がんメカニズムの解明へとつながり、新しい発がんの予防法やがん治療法の開発へと貢献できるものであると考える。