The γH2AX DSB marker may not be a suitable biodosimeter to measure the biological MRT valley dose,International Journal of Radiation Biology

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The γH2AX DSB marker may not be a suitable biodosimeter to measure the biological MRT valley dose
International Journal of Radiation Biology ( IF 2.1 ) Pub Date : 2021-03-15 , DOI: 10.1080/09553002.2021.1893854
Jessica A Ventura ₁ , Jacqueline F Donoghue ₁ , Cameron J Nowell ₂ , Leonie M Cann ₁ , Liam R J Day ₃ , Lloyd M L Smyth ₁ , Helen B Forrester _{3,

4,

5} , Peter A W Rogers ₁ , Jeffrey C Crosbie ₃

Affiliation

Abstract

Purpose

γH2AX biodosimetry has been proposed as an alternative dosimetry method for microbeam radiation therapy (MRT) because conventional dosimeters, such as ionization chambers, lack the spatial resolution required to accurately measure the MRT valley dose. Here we investigated whether γH2AX biodosimetry should be used to measure the biological valley dose of MRT-irradiated mammalian cells.

Materials and methods

We irradiated human skin fibroblasts and mouse skin flaps with synchrotron MRT and broad beam (BB) radiation. BB doses of 1–5 Gy were used to generate a calibration curve in order to estimate the biological MRT valley dose using the γH2AX assay.

Results

Our key finding was that MRT induced a non-linear dose response compared to BB, where doses 2–3 times greater showed the same level of DNA DSB damage in the valley in cell and tissue studies. This indicates that γH2AX may not be an appropriate biodosimeter to estimate the biological valley doses of MRT-irradiated samples. We also established foci yields of 5.9 ± $0.04$ and 27.4 ± $2.5$ foci/cell/Gy in mouse skin tissue and human fibroblasts respectively, induced by BB. Using Monte Carlo simulations, a linear dose response was seen in cell and tissue studies and produced predicted peak-to-valley dose ratios (PVDRs) of ∼30 and ∼107 for human fibroblasts and mouse skin tissue respectively.

Conclusions

Our report highlights novel MRT radiobiology, attempts to explain why γH2AX may not be an appropriate biodosimeter and suggests further studies aimed at revealing the biological and cellular communication mechanisms that drive the normal tissue sparing effect, which is characteristic of MRT.

中文翻译：

γH2AX DSB 标记可能不是测量生物 MRT 谷剂量的合适生物剂量计

抽象的

目的

γH2AX 生物剂量测定法已被提议作为微束放射治疗 (MRT) 的替代剂量测定方法，因为传统剂量计（例如电离室）缺乏精确测量 MRT 谷剂量所需的空间分辨率。在这里，我们研究了是否应该使用 γH2AX 生物剂量测定法来测量 MRT 照射的哺乳动物细胞的生物谷剂量。

材料和方法

我们用同步加速器 MRT 和宽束 (BB) 辐射照射人类皮肤成纤维细胞和小鼠皮瓣。使用 1-5 Gy 的 BB 剂量生成校准曲线，以便使用 γH2AX 测定估计生物 MRT 谷剂量。

结果

我们的主要发现是，与 BB 相比，MRT 引起了非线性剂量反应，在细胞和组织研究中，2-3 倍的剂量显示出相同水平的 DNA DSB 损伤。这表明 γH2AX 可能不是合适的生物剂量计来估计 MRT 辐照样品的生物谷剂量。我们还确定焦点产量为 5.9 ± $0 。 04$ 和 27.4 ± $2 。 5$ BB 诱导的小鼠皮肤组织和人成纤维细胞中分别具有 foci/cell/Gy。使用蒙特卡罗模拟，在细胞和组织研究中观察到线性剂量响应，并产生人类成纤维细胞和小鼠皮肤组织的预测峰谷剂量比（PVDR）分别为~30和~107。