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マイクロドジメトリに基づく標的・非標的効果を同時に考慮可能な細胞生存率評価モデル

Model for estimating cell surviving fraction for both targeted and nontargeted effects on the basis of microdosimetry

佐藤 達彦; 浜田 信行*

Sato, Tatsuhiko; Hamada, Nobuyuki*

原子力機構では、粒子・重イオン輸送計算コードPHITSを用いて、放射線照射による物理的な吸収線量のみならず、その生物学的な効果を反映した生物学的線量評価モデルの開発を行っている。本研究では、様々な線種の電離放射線に照射された細胞生存率を、細胞核が直接照射されることにより致死に至る標的効果と、別の照射細胞から発信されたアポトーシスシグナルを受信することにより致死に至る非標的効果を同時に考慮して計算可能な新たなモデルを開発した。そのモデルでは、放射線場を特徴づけるための指標として、従来のモデルでよく使われてきたマクロ吸収線量やLETではなく、PHITSで計算した各細胞核及びそのクロマチンドメインにおけるミクロ吸収線量の確率密度分布を用いる。開発したモデルによる計算結果と、過去において測定された様々な生物実験結果を比較したところ、モデル計算は照射条件(線量やLETなど)や照射方法(マイクロビームやブロードビーム)に関わらず生物実験データを再現可能であることが分かった。本発表では、PHITSによるミクロ吸収線量の計算方法とモデルの概要について紹介する。

We here propose a new model assembly for estimating the surviving fraction of cells irradiated with various types of ionizing radiation, considering both targeted and nontargeted effects in the same framework. The probability densities of specific energies in two scales, which are the cell nucleus and its substructure called a domain, were employed as the physical index for characterizing the radiation fields. In the model assembly, our previously established double stochastic microdosimetric kinetic (DSMK) model was used to express the targeted effect, whereas a newly developed model was used to express the nontargeted effect. The radioresistance caused by overexpression of anti-apoptotic protein Bcl-2 known to frequently occur in human cancer was also considered by introducing the concept of the adaptive response in the DSMK model. The accuracy of the model assembly was examined by comparing the computationally and experimentally determined surviving fraction of Bcl-2 cells (Bcl-2 overexpressing HeLa cells) and Neo cells (neomycin resistant gene-expressing HeLa cells) irradiated with microbeam or broadbeam of energetic heavy ions, as well as the WI-38 normal human fibroblasts irradiated with X-ray microbeam. The model assembly reproduced very well the experimentally determined surviving fraction over a wide range of dose and linear energy transfer (LET) values. Our newly established model assembly will be worth being incorporated into treatment planning systems for heavy-ion therapy, brachytherapy, and boron neutron capture therapy, given critical roles of the frequent Bcl-2 overexpression and the nontargeted effect in estimating therapeutic outcomes and harmful effects of such advanced therapeutic modalities.

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