Minami Kazumasa, Yagi Masashi, Fujita Kazuki, Nagata Kana, Hidani Ryo, Hamatani Noriaki, Tsubouchi Toshiro, Takashina Masaaki, Umezawa Masumi, Nomura Takuya, Shimizu Masaki, Kuwana Yoshiaki, Fujimoto Jiro, Shimizu Shinichi, Ogawa Kazuhiko
Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Carbon Ion Radiotherapy, Osaka University Graduate School of Medicine, Osaka, Japan;
Anticancer Res. 2025 Mar;45(3):955-963. doi: 10.21873/anticanres.17483.
BACKGROUND/AIM: Ultra-high dose rate irradiation (uHDR) (>40 Gy/s), commonly referred to as FLASH, has garnered attention in radiation therapy research due to its potential to mitigate damage to normal tissues while maintaining tumoricidal effects. Research on FLASH therapy using electron beams, X-rays, and proton beams has preceded studies using carbon ion beams. However, the clinical potential of FLASH carbon ion irradiation is increasingly being recognized, similar to other radiation modalities. This study aimed to evaluate the cell-sparing effect of carbon ion beams under normoxic conditions - a phenomenon that has not been previously reported.
Human salivary gland cell line (HSGc-c5), human dermal fibroblast (HDF) and human lung bronchial epithelial cell line (Nuli-1) were employed. In this study, we compared two types of linear energy transfer (19 and 50 keV/μm) and two oxygen concentrations (4% and 21%) to thoroughly investigate the cell-sparing effect, with cell death as the endpoint.
A significant cell-sparing effect was observed with carbon ion beam uHDR irradiation under normoxic conditions. Linear energy transfer (LET) influenced the manifestation of the sparing effect, with higher LET (50 keV/μm) demonstrating a stronger protective effect compared to lower LET (19 keV/μm). DNA damage, as indicated by γH2AX foci, was significantly reduced under uHDR compared to conventional dose rates.
Carbon ion uHDR irradiation induces a cell-sparing effect under normoxic conditions, which is influenced by LET and oxygen concentration. These findings provide essential insights into the mechanisms underlying the FLASH effect and pave the way for advancing the clinical application of uHDR carbon ion therapy.
背景/目的：超高剂量率照射（uHDR）（>40 Gy/s），通常称为FLASH，因其在保持杀瘤效果的同时减轻对正常组织损伤的潜力，在放射治疗研究中受到关注。使用电子束、X射线和质子束的FLASH治疗研究先于使用碳离子束的研究。然而，与其他放射模式类似，FLASH碳离子照射的临床潜力正日益得到认可。本研究旨在评估常氧条件下碳离子束的细胞保护效应——这是一种此前未被报道的现象。
使用人唾液腺细胞系（HSGc-c5）、人皮肤成纤维细胞（HDF）和人肺支气管上皮细胞系（Nuli-1）。在本研究中，我们比较了两种线性能量传递（19和50 keV/μm）和两种氧浓度（4%和21%），以全面研究细胞保护效应，以细胞死亡作为终点。
在常氧条件下，碳离子束uHDR照射观察到显著的细胞保护效应。线性能量传递（LET）影响保护效应的表现，与较低LET（19 keV/μm）相比，较高LET（50 keV/μm）显示出更强的保护作用。与传统剂量率相比，uHDR下γH2AX焦点所示的DNA损伤显著减少。
碳离子uHDR照射在常氧条件下诱导细胞保护效应，该效应受LET和氧浓度影响。这些发现为FLASH效应的潜在机制提供了重要见解，并为推进uHDR碳离子治疗的临床应用铺平了道路。
