Construction of mathematical models for the biological effects of low-dose and low-dose-rate radiation assuming cell competition and replication errors

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K19972
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 63020:Radiation influence-related
• Research Institution: Central Research Institute of Electric Power Industry
• Principal Investigator: Uchinomiya Kouki 一般財団法人電力中央研究所, サステナブルシステム研究本部, 主任研究員 (40784426)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 低線量率放射線 / 数理モデル / 細胞競合 / 発がんリスク / 進化ゲーム理論 / 多段階発がんモデル

Outline of Final Research Achievements

The mathematical model showed that the risks of many cancers could be explained by replication errors. In some cancers, the estimated parameters were excessively high compared to the results of previous studies. When external factors were taken into account, the mathematical model could explain the cancer risks within parameter ranges consistent with existing knowledge. I also showed whether the accumulation of radiation-induced damage is suppressed or promoted by stem cell competition may qualitatively differ depending not only on the properties of the cells but also on the total number of cells in the cell pool and the spatial structure. Furthermore, by considering replication errors, DNA damage due to external factors, and cell competition together, I have constructed a mathematical model that lays the foundation for analyzing how low-dose and low-dose-rate radiation affects cancer risk.

Free Research Field

数理生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、基礎生物学、放射線防護、医療などの放射線利用を考える面においても重要である一方、検出が難しく十分解明されていない低線量・低線量率放射線の発がんへの影響を捉えるための基盤となる数理モデルを開発した。複製エラーと外的要因によるDNA損傷を考慮することで、複製エラーを基準として放射線などの外的要因によってどれだけ発がんリスクが上昇するかを議論できる。また、低線量・低線量率被ばくにおいて重要だと考えられる幹細胞競合を考えることで、放射線発がんをより一般的に捉えることができる。