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A Mathematical model of radiation-induced responses in a cellular population including cell-to-cell communications

細胞間コミュニケーションを考慮した細胞集団の放射線応答モデル

服部 佑哉; 鈴木 芳代; 舟山 知夫; 小林 泰彦; 横谷 明徳; 渡辺 立子

Hattori, Yuya; Suzuki, Michiyo; Funayama, Tomoo; Kobayashi, Yasuhiko; Yokoya, Akinari; Watanabe, Ritsuko

本研究では、細胞集団中の細胞間シグナル伝達と細胞周期の時間・空間的な動態を計算可能な数理モデルを構築し、照射する放射線の線量や照射領域によってシグナル伝達がどのように変化するのか、その結果、放射線応答として細胞周期や細胞の生存にどのような変化が現れるのかを明らかにすることを目的とする。提案する放射線応答モデルでは、細胞間のシグナルをギャップ結合経由のシグナルX、培養液経由のシグナルYとし、これら2つのシグナル伝達を誘発する放射線をシグナルZとして表現する。個々の細胞の細胞周期は、周期的な進行(G1, S, G2, M期)がシグナルX, Y, Zによって停止する仮想時計として表現する。講演では、2次元平面上に配置された細胞集団にシグナルZが入力されたとき、シグナルX, Yが拡散方程式に基づいて集団全体に伝達する様子と、各シグナルによって仮想時計(細胞周期)が変化する様子について、線量や照射領域を変えた計算結果の一例を示し、放射線応答の解析に対する本モデルの有用性を報告する。

Cell-to-cell communication is one of the important factors to understand the mechanisms of radiation-induced responses such as radiation-induced bystander effects at low doses. In the present study, we propose simulation-based analyses of the intercellular signal transmissions between the individual cells in the cellular population. We developed the transmissions of two types of signals, i.e., X is transmitted via culture medium and Y is transmitted via gap junctions based on the diffusion equation. To observe the cell cycle as the response of cell induced by the signals, X and Y, we represented the cell cycle as a virtual clock including several check-point pathways and the cyclic process (G1, S, G2, M phases). The cellular population was divided into the grids (cells), and the signals and the clock were calculated for each grid. The signals, X, Y, were transmitted to the cells and stopped the clocks at the check points. Furthermore, the radiation was modeled as the radiation signal, Z, which affected the clock and the signals, X and Y. We input the radiation signal, Z, to specific cells, and simulated the behaviors of the clock of each cell and signals, X and Y. We will discuss the usefulness of our model for investigating the mechanisms of radiation-induced responses of the cell cycle via cell-to-cell communications.

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パーセンタイル:53.75

分野:Environmental Sciences

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