Kondo Natsuko, Michiue Hiroyuki, Sakurai Yoshinori, Tanaka Hiroki, Nakagawa Yosuke, Watanabe Tsubasa, Narabayashi Masaru, Kinashi Yuko, Suzuki Minoru, Masunaga Shin-Ichiro, Ono Koji
Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Osaka, Japan.
Department of Physiology, Okayama University, Okayama, Japan.
Rep Pract Oncol Radiother. 2016 Mar-Apr;21(2):108-12. doi: 10.1016/j.rpor.2014.10.005. Epub 2014 Oct 31.
In this study, we investigated γH2AX foci as markers of DSBs in normal brain and brain tumor tissue in mouse after BNCT.
Boron neutron capture therapy (BNCT) is a particle radiation therapy in combination of thermal neutron irradiation and boron compound that specifically accumulates in the tumor. (10)B captures neutrons and produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). These particles have the characteristics of extremely high linear energy transfer (LET) radiation and therefore have marked biological effects. High LET radiation causes severe DNA damage, DNA DSBs. As the high LET radiation induces complex DNA double strand breaks (DSBs), large proportions of DSBs are considered to remain unrepaired in comparison with exposure to sparsely ionizing radiation.
We analyzed the number of γH2AX foci by immunohistochemistry 30 min or 24 h after neutron irradiation.
In both normal brain and brain tumor, γH2AX foci induced by (10)B(n,α)(7)Li reaction remained 24 h after neutron beam irradiation. In contrast, γH2AX foci produced by γ-ray irradiation at contaminated dose in BNCT disappeared 24 h after irradiation in these tissues.
DSBs produced by (10)B(n,α)(7)Li reaction are supposed to be too complex to repair for cells in normal brain and brain tumor tissue within 24 h. These DSBs would be more difficult to repair than those by γ-ray. Excellent anti-tumor effect of BNCT may result from these unrepaired DSBs induced by (10)B(n,α)(7)Li reaction.
在本研究中，我们研究了γH2AX病灶作为硼中子俘获疗法（BNCT）后小鼠正常脑和脑肿瘤组织中双链断裂（DSB）的标志物。
硼中子俘获疗法（BNCT）是一种将热中子辐照与特异性聚集在肿瘤中的硼化合物相结合的粒子放射疗法。硼-10（¹⁰B）俘获中子并产生一个α粒子（氦-4，⁴He）和一个反冲锂核（锂-7，⁷Li）。这些粒子具有极高的线性能量传递（LET）辐射的特性，因此具有显著的生物学效应。高LET辐射会导致严重的DNA损伤，即DNA双链断裂（DSB）。由于高LET辐射会诱导复杂的DNA双链断裂，与受到低LET辐射相比，很大比例的DSB被认为仍未得到修复。
我们在中子辐照后30分钟或24小时通过免疫组织化学分析γH2AX病灶的数量。
在正常脑和脑肿瘤中，硼-10（¹⁰B）（n，α）（⁷Li）反应诱导产生的γH2AX病灶在中子束辐照后24小时仍然存在。相比之下，在BNCT中受污染剂量的γ射线辐照产生的γH2AX病灶在这些组织辐照后24小时消失。
硼-10（¹⁰B）（n，α）（⁷Li）反应产生的DSB对于正常脑和脑肿瘤组织中的细胞来说，在24小时内被认为过于复杂而无法修复。这些DSB比γ射线产生的DSB更难修复。BNCT出色的抗肿瘤效果可能源于硼-10（¹⁰B）（n，α）（⁷Li）反应诱导产生的这些未修复的DSB。
