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Performance Evaluation for Repair of HSGc-C5 Carcinoma Cell Using Geant4-DNA

使用 Geant4-DNA 修復(fù) HSGc-C5 癌細(xì)胞的性能評(píng)估

To evaluate the repair performance of HSGc-C5 carcinoma cell against radiation-induced DNA damage, a Geant4-DNA application for radiobiological research was extended by using newly measured experimental data acquired in this study. Concerning fast- and slow-DNA rejoining, the two-lesion kinetics (TLK) model parameters were adequately optimized (the repair speeds of each process were reasonably close to the DNA rejoining speed of the nonhomologous end-joining and homologous recombination pathways). The lethality probabilities of the DNA damage induced by complex double strand breaks (DSBs) and binary repair were approximately 3% and 40%, respectively. Using the optimized repair parameters, the Geant4-DNA simulation was able to predict the cell surviving fraction (SF) and the DNA repair kinetics.

為了評(píng)估 HSGc-C5 癌細(xì)胞對(duì)輻射誘導(dǎo)的 DNA 損傷的修復(fù)性能，通過(guò)使用本研究中獲得的新測(cè)量的實(shí)驗(yàn)數(shù)據(jù)，擴(kuò)展了 Geant4-DNA 在放射生物學(xué)研究中的應(yīng)用。在快速和慢速 DNA 重新連接方面，雙損傷動(dòng)力學(xué) (TLK) 模型參數(shù)得到了充分優(yōu)化（每個(gè)過(guò)程的修復(fù)速度合理地接近非同源末端連接和同源重組途徑的 DNA 重新連接速度）。復(fù)雜雙鏈斷裂 (DSB) 和二元修復(fù)誘導(dǎo)的 DNA 損傷的致死概率約為3 % 和 40 %， 分別。使用優(yōu)化的修復(fù)參數(shù)，Geant4-DNA 模擬能夠預(yù)測(cè)細(xì)胞存活分?jǐn)?shù) (SF) 和 DNA 修復(fù)動(dòng)力學(xué)。

10層細(xì)胞工廠

Track-structure Monte Carlo simulations are useful tools to evaluate initial DNA damage induced by irradiation. In the previous study, we have developed a Gean4-DNA-based application to estimate the cell surviving fraction of V79 cells after irradiation, bridging the gap between the initial DNA damage and the DNA rejoining kinetics by means of the two-lesion kinetics (TLK) model. However, since the DNA repair performance depends on cell line, the same model parameters cannot be used for different cell lines. Thus, we extended the Geant4-DNA application with a TLK model for the evaluation of DNA damage repair performance in HSGc-C5 carcinoma cells which are typically used for evaluating proton/carbon radiation treatment effects. For this evaluation, we also performed experimental measurements for cell surviving fractions and DNA rejoining kinetics of the HSGc-C5 cells irradiated by 70 MeV protons at the cyclotron facility at the National Institutes for Quantum and Radiological Science and Technology (QST). Concerning fast- and slow-DNA rejoining, the TLK model parameters were adequately optimized with the simulated initial DNA damage. The optimized DNA rejoining speeds were reasonably agreed with the experimental DNA rejoining speeds. Using the optimized TLK model, the Geant4-DNA simulation is now able to predict cell survival and DNA-rejoining kinetics for HSGc-C5 cells. View Full-Text。

高效搖瓶

軌道結(jié)構(gòu)蒙特卡羅模擬是評(píng)估輻射引起的初始 DNA 損傷的有用工具。在之前的研究中，我們開(kāi)發(fā)了一種基于 Gean4-DNA 的應(yīng)用程序來(lái)估計(jì)輻照后 V79 細(xì)胞的細(xì)胞存活率，通過(guò)雙損傷動(dòng)力學(xué)（TLK）彌合初始 DNA 損傷和 DNA 重新連接動(dòng)力學(xué)之間的差距） 模型。然而，由于 DNA 修復(fù)性能取決于細(xì)胞系，相同的模型參數(shù)不能用于不同的細(xì)胞系。因此，我們使用 TLK 模型擴(kuò)展了 Geant4-DNA 應(yīng)用，用于評(píng)估 HSGc-C5 癌細(xì)胞中的 DNA 損傷修復(fù)性能，這些細(xì)胞通常用于評(píng)估質(zhì)子/碳輻射治療效果。對(duì)于本次評(píng)測(cè)，我們還在美國(guó)國(guó)家量子與放射科學(xué)與技術(shù)研究所 (QST) 的回旋加速器設(shè)施中對(duì) 70 MeV 質(zhì)子照射的 HSGc-C5 細(xì)胞的細(xì)胞存活部分和 DNA 重新加入動(dòng)力學(xué)進(jìn)行了實(shí)驗(yàn)測(cè)量。關(guān)于快速和慢速 DNA 重新加入，TLK 模型參數(shù)通過(guò)模擬的初始 DNA 損傷進(jìn)行了充分優(yōu)化。優(yōu)化的 DNA 重新加入速度與實(shí)驗(yàn) DNA 重新加入速度合理一致。使用優(yōu)化的 TLK 模型，Geant4-DNA 模擬現(xiàn)在能夠預(yù)測(cè) HSGc-C5 細(xì)胞的細(xì)胞存活和 DNA 重新連接動(dòng)力學(xué)。使用模擬的初始 DNA 損傷對(duì) TLK 模型參數(shù)進(jìn)行了充分優(yōu)化。優(yōu)化的 DNA 重新加入速度與實(shí)驗(yàn) DNA 重新加入速度合理一致。使用優(yōu)化的 TLK 模型，Geant4-DNA 模擬現(xiàn)在能夠預(yù)測(cè) HSGc-C5 細(xì)胞的細(xì)胞存活和 DNA 重新連接動(dòng)力學(xué)。使用模擬的初始 DNA 損傷對(duì) TLK 模型參數(shù)進(jìn)行了充分優(yōu)化。優(yōu)化的 DNA 重新加入速度與實(shí)驗(yàn) DNA 重新加入速度合理一致。使用優(yōu)化的 TLK 模型，Geant4-DNA 模擬現(xiàn)在能夠預(yù)測(cè) HSGc-C5 細(xì)胞的細(xì)胞存活和 DNA 重新連接動(dòng)力學(xué)。

關(guān)鍵詞：Geant4-DNA,DNA repair,cell surviving fraction Geant4-DNA,DNA修復(fù),細(xì)胞存活分?jǐn)?shù)

來(lái)源：MDPI https://www.mdpi.com/2072-6694/13/23/6046/htm