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重点关注 DNA 损伤与修复的高传能线密度放射疗法相关的关键生物学机制。

Key biological mechanisms involved in high-LET radiation therapies with a focus on DNA damage and repair.

机构信息

Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou Campus, 15780Athens, Greece.

Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104USA.

出版信息

Expert Rev Mol Med. 2022 Mar 31;24:e15. doi: 10.1017/erm.2022.6.

DOI:10.1017/erm.2022.6
PMID:35357290
Abstract

DNA damage and repair studies are at the core of the radiation biology field and represent also the fundamental principles informing radiation therapy (RT). DNA damage levels are a function of radiation dose, whereas the type of damage and biological effects such as DNA damage complexity, depend on radiation quality that is linear energy transfer (LET). Both levels and types of DNA damage determine cell fate, which can include necrosis, apoptosis, senescence or autophagy. Herein, we present an overview of current RT modalities in the light of DNA damage and repair with emphasis on medium to high-LET radiation. Proton radiation is discussed along with its new adaptation of FLASH RT. RT based on α-particles includes brachytherapy and nuclear-RT, that is proton-boron capture therapy (PBCT) and boron-neutron capture therapy (BNCT). We also discuss carbon ion therapy along with combinatorial immune-based therapies and high-LET RT. For each RT modality, we summarise relevant DNA damage studies. Finally, we provide an update of the role of DNA repair in high-LET RT and we explore the biological responses triggered by differential LET and dose.

摘要

DNA 损伤与修复研究是放射生物学领域的核心,也是放射治疗(RT)的基本原理。DNA 损伤水平是辐射剂量的函数,而损伤类型和生物学效应,如 DNA 损伤复杂性,则取决于线性能量转移(LET)的辐射质量。DNA 损伤的水平和类型决定了细胞命运,包括坏死、凋亡、衰老或自噬。在此,我们根据 DNA 损伤和修复的情况概述了当前的 RT 方式,重点介绍了中高能 LET 辐射。我们讨论了质子辐射及其 FLASH RT 的新应用。基于 α 粒子的 RT 包括近距离放射治疗和核 RT,即质子-硼俘获治疗(PBCT)和硼-中子俘获治疗(BNCT)。我们还讨论了碳离子治疗以及组合免疫治疗和高 LET RT。对于每种 RT 方式,我们总结了相关的 DNA 损伤研究。最后,我们提供了关于高 LET RT 中 DNA 修复作用的最新信息,并探讨了不同 LET 和剂量引发的生物学反应。

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