Department of Environmental Health, National Institute of Public Health, Saitama, 351-0197, Japan.
J Radiat Res. 2021 May 5;62(Supplement_1):i36-i43. doi: 10.1093/jrr/rraa090.
The health risks associated with low-dose radiation, which are a major concern after the Fukushima Daiichi nuclear power plant accident (the Fukushima accident), have been extensively investigated, and the cancer risks from low-dose radiation exposure (below ~ 100 mSv) are thought to be negligible. According to World Health Organization and the United Nations Scientific Committee on the Effects of Atomic Radiation reports, the level of radiation exposure from the Fukushima accident is limited, estimating no significant increased risk from the accident. Radiation-induced cell injury is mainly caused by oxidative damage to biomolecules, including DNA, lipids and proteins. Radiation stimulates metabolic activation within the mitochondria to provide energy for the DNA damage response. Mitochondrial respiratory chain complexes I and III are the most important intracellular source of reactive oxygen species (ROS) during oxidative phosphorylation in eukaryotic cells. Manganese superoxide dismutase and glutathione are key players in redox control within cells. However, perturbation of the antioxidant response leads to chronic oxidative stress in irradiated cells. Excess ROS of mitochondrial origin is reported in cancer-associated fibroblast and promotes carcinogenesis. The aim of this review paper is to discuss critical roles of mitochondria in radiation-related cancer by introducing our recent studies. In particular, elevated mitochondrial ROS in stromal fibroblasts potentiate transforming growth factor-beta (TGF-β) signaling, which triggers smooth muscle actin (α-SMA) expression to stimulate myofibroblast differentiation. Radiation-induced myofibroblasts promote tumor growth by enhancing angiogenesis. Thus, radiation affects both malignant cancer cells and neighboring stromal cells through secretion of soluble factors.
福岛第一核电站事故（福岛事故）后，人们广泛研究了与低剂量辐射相关的健康风险，认为低剂量辐射暴露（低于~100mSv）的致癌风险可以忽略不计。根据世界卫生组织和联合国原子辐射影响问题科学委员会的报告，福岛事故的辐射照射水平有限，估计事故不会带来显著的额外风险。辐射诱导的细胞损伤主要是由生物分子（包括 DNA、脂质和蛋白质）的氧化损伤引起的。辐射刺激线粒体中的代谢激活，为 DNA 损伤反应提供能量。在线粒体氧化磷酸化过程中，呼吸链复合物 I 和 III 是真核细胞中活性氧（ROS）的最重要的内源性来源。锰超氧化物歧化酶和谷胱甘肽是细胞内氧化还原控制的关键因素。然而，抗氧化反应的失调会导致辐照细胞发生慢性氧化应激。据报道，源自线粒体的过量 ROS 存在于与癌症相关的成纤维细胞中，并促进致癌作用。本文旨在通过介绍我们的最新研究，讨论线粒体在与辐射相关的癌症中的关键作用。特别是，基质成纤维细胞中升高的线粒体 ROS 增强了转化生长因子-β（TGF-β）信号，触发平滑肌肌动蛋白（α-SMA）表达，从而刺激肌成纤维细胞分化。辐射诱导的肌成纤维细胞通过促进血管生成来促进肿瘤生长。因此，辐射通过分泌可溶性因子影响恶性癌细胞和邻近的基质细胞。
