In vitro validation of helium ion irradiations as a function of linear energy transfer in radioresistant human malignant cells.

Aleksandra M Ristić Fira, Otilija D Keta, Vladana D Petković, Miloš Đorđević, Giada Petringa, Serena Fattori, Roberto Catalano, Giuseppe Pablo Cirrone, Giacomo Cuttone, Dousatsu Sakata, Ngoc Hoang Tran, Konstantinos Chatzipapas, Sebastien Incerti, Ivan M Petrović
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Abstract

Purpose: Based on considerable interest to enlarge the experimental database of radioresistant cells after their irradiation with helium ions, HTB140, MCF-7 and HTB177 human malignant cells are exposed to helium ion beams having different linear energy transfer (LET).

Materials and methods: The cells are irradiated along the widened 62 MeV/u helium ion Bragg peak, providing LET of 4.9, 9.8, 23.4 and 36.8 keV/µm. Numerical simulations with the Geant4 toolkit are used for the experimental design. Cell survival is evaluated and compared with reference γ-rays. DNA double strand breaks are assessed via γ-H2AX foci.

Results: With the increase of LET, surviving fractions at 2 Gy decrease, while RBE (2 Gy, γ) gradually increase. For HTB140 cells, above the dose of 4 Gy, a slight saturation of survival is observed while the increase of RBE (2 Gy, γ) remains unaffected. With the increase of LET the increase of γ-H2AX foci is revealed at 0.5 h after irradiation. There is no significant difference in the number of foci between the cell lines for the same LET. From 0.5 to 24 h, the number of foci drops reaching its residual level. For each time point, there are small differences in DNA DSB among the three cell lines.

Conclusion: Analyses of data acquired for the three cell lines irradiated by helium ions, having different LET, reveal high elimination capacity and creation of a large number of DNA DSB with respect to γ-rays, and are between those reported for protons and carbon ions.

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体外验证氦离子辐照在抗放射人类恶性细胞中的线性能量传递函数。
目的:基于对扩大氦离子照射抗放射细胞实验数据库的浓厚兴趣,HTB140、MCF-7和HTB177人类恶性细胞暴露于不同线性能量转移(LET)的氦离子束:细胞沿扩大的 62 MeV/u 氦离子布拉格峰照射,LET 分别为 4.9、9.8、23.4 和 36.8 keV/µm。实验设计采用 Geant4 工具包进行数值模拟。对细胞存活率进行评估,并与参考γ射线进行比较。通过γ-H2AX病灶评估DNA双链断裂情况:结果:随着 LET 的增加,2 Gy 存活率下降,而 RBE(2 Gy,γ)逐渐增加。对于 HTB140 细胞,当剂量超过 4 Gy 时,存活率出现轻微饱和,而 RBE(2 Gy,γ)的增加不受影响。随着 LET 的增加,γ-H2AX 病灶在照射后 0.5 h 出现增加。在相同的 LET 下,不同细胞系的病灶数量没有明显差异。从 0.5 到 24 小时,病灶数量下降到残余水平。在每个时间点,三种细胞系之间的 DNA DSB 差异很小:对不同LET的氦离子照射三种细胞系所获得的数据进行分析后发现,与γ射线相比,氦离子具有较高的消除能力,并能产生大量DNA DSB,介于质子和碳离子之间。
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