Department of Radiation Medical Sciences, Nagasaki University Atomic Bomb Disease Institute. 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Life Sciences and Radiation Research, Graduate School of Biomedical Sciences, Nagasaki University. 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
J Radiat Res. 2021 May 5;62(Supplement_1):i30-i35. doi: 10.1093/jrr/rraa086.
DNA double-strand breaks (DSBs) induced by ionizing radiation are the major cause of cell death, leading to tissue/organ injuries, which is a fundamental mechanism underlying the development of tissue reaction. Since unscheduled senescence, predominantly induced among epithelial tissues/organs, is one of the major modes of cell death in response to radiation exposure, its role in tissue reaction has been extensively studied, and it has become clear that senescence-mediated secretion of soluble factors is an indispensable component of the manifestation of tissue reaction. Recently, an unexpected link between cytoplasmic DSBs and innate immunity was discovered. The activation of cyclic GMP-AMP (cGAMP) synthase (cGAS) results in the stimulation of the cGAS-stimulator of interferon genes (STING) pathway, which has been shown to regulate the transactivation of a variety of secretory factors that are the same as those secreted from senescent cells. Furthermore, it has been proven that cGAS-STING pathway also mediates execution of the senescence process by itself. Hence, an autocrine/paracrine feedback loop has been discussed in previous literature in relation to its effect on the tissue microenvironment. As the tissue microenvironment plays a crucial role in cancer development, tissue reaction could be involved in the late health effects caused by radiation exposure. In this paper, the novel findings in radiation biology, which should provide a better understanding of the mechanisms underlying radiation-induced carcinogenesis, are overviewed.
DNA 双链断裂（DSBs）是电离辐射诱导的细胞死亡的主要原因，导致组织/器官损伤，这是组织反应发展的基本机制。由于未计划的衰老，主要发生在上皮组织/器官中，是对辐射暴露的主要细胞死亡模式之一，因此其在组织反应中的作用已被广泛研究，并且已经清楚衰老介导的可溶性因子的分泌是组织反应表现的不可或缺的组成部分。最近，细胞质 DSBs 与先天免疫之间发现了一个意外的联系。环鸟苷酸-AMP（cGAMP）合酶（cGAS）的激活导致干扰素基因刺激因子（STING）途径的刺激，该途径已被证明可调节与衰老细胞分泌的相同的多种分泌因子的反式激活。此外，已经证明 cGAS-STING 途径本身也介导衰老过程的执行。因此，在之前的文献中讨论了自分泌/旁分泌反馈回路，因为它对组织微环境有影响。由于组织微环境在癌症发展中起着至关重要的作用，因此组织反应可能涉及辐射暴露引起的晚期健康影响。本文综述了放射生物学的新发现，这应该有助于更好地理解辐射诱导致癌的机制。
