Biological effects in normal cells exposed to FLASH dose rate protons

克隆形成试验 辐照 核医学 放射生物学 质子 毒性 剂量率 放射治疗 医学 细胞 化学 癌症研究 放射化学 内科学 生物化学 物理 量子力学 核物理学
作者
Manuela Buonanno,Veljko Grilj,David J. Brenner
出处
期刊:Radiotherapy and Oncology [Elsevier BV]
卷期号:139: 51-55 被引量:201
标识
DOI:10.1016/j.radonc.2019.02.009
摘要

Background Radiotherapy outcomes are limited by toxicity in the healthy tissues surrounding the irradiated tumor. Recent pre-clinical studies have shown that irradiations with electrons or photons delivered at so called FLASH dose rates (i.e. >40 Gy/s) dramatically reduce adverse side effects in the normal tissues while being equally efficient for tumor control as irradiations at conventional dose rates (3–5 cGy/s). In the case of protons however, FLASH effects have not been investigated partially because of the limited availability of facilities that can achieve such high dose rates. Methods Using a novel irradiation platform, we measured acute and long-term biological effects in normal human lung fibroblasts (IMR90) exposed to therapeutically relevant doses of 4.5 MeV protons (LET = 10 keV/µm) delivered at dose rates spanning four orders of magnitude. Endpoints included clonogenic cell survival, γH2AX foci formation, induction of premature senescence (β-gal), and the expression of the pro-inflammatory marker TGFβ. Results Proton dose rate had no influence on the cell survival, but for the highest dose rate used (i.e. 1000 Gy/s) foci formation saturated beyond 10 Gy. In the progeny of irradiated cells, an increase in dose (20 Gy vs. 10 Gy) and dose rate (1000 Gy/s vs. 0.05 Gy/s) positively affected the number of senescence cells and the expression of TGFβ1. Conclusions In normal lung fibroblasts proton dose rate had little impact on acute effects, but significantly influenced the expression of long-term biological responses in vitro. Compared to conventional dose rates, protons delivered at FLASH dose rates mitigated such delayed detrimental effects.
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