Kohzaki Masaoki, Ootsuyama Akira, Abe Toshiaki, Tsukamoto Manabu, Umata Toshiyuki, Okazaki Ryuji
Department of Radiobiology and Hygiene Management Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health Kitakyushu Japan.
Department of Radiation Biology and Health School of Medicine, University of Occupational and Environmental Health Kitakyushu Japan.
JBMR Plus. 2022 Dec 3;6(12):e10688. doi: 10.1002/jbm4.10688. eCollection 2022 Dec.
Ionizing radiation (IR) is a well-known carcinogen. High-dose-rate (HDR) IR is known to damage long bones (in terms of mass and structure), but the relationships among dose rates (particularly low-dose-rate [LDR] IR), long-bone condition, cancer incidence, and lifespan shortening remain elusive. The aim of this study was to elucidate the effects of LDR-IR on long-bone condition by comparing the long-term consequences of HDR- and LDR-IR exposure in mice. We utilized micro-computed tomography (μCT) scans of the long bones at similar ages (mean 77-96 weeks) to compare mice receiving approximately equivalent total doses of internal LDR-IR or external HDR-IR starting at 4 weeks of age, and their respective control groups. The lifespan-shortening effects of LDR-IR and HDR-IR were similar in these mixed-sex cohorts. Notably, compared to HDR-IR mice, mice internally exposed to chronic LDR-IR with continuous hypohematopoiesis showed a significantly higher trabecular bone connective density [femur: 247% ( = 0.0042), tibia: 169% ( = 0.0005)] and midshaft cortical bone thickness/area (femur: 130% [ = 0.0079]/120% [ = 0.021], tibia: 148% [ = 0.0004]/129% [ = 0.002]). Consistent with this result, when comparing 26-32 weeks post-IR with 2-8 weeks post-IR, compared to HDR-IR-treated mice, LDR-IR-treated mice exhibited higher levels of an osteoblast marker (OPG; = 0.67 for HDR-IR, = 0.068 for LDR-IR) and lower levels of an osteoclast marker (CTX-I; = 0.0079 for HDR-IR, = 0.72 for LDR-IR) despite significantly higher levels of inflammatory markers (CCL2 and CXCL1; = 0.36-0.8 for HDR-IR, = 0.013-0.041 for LDR-IR). These results suggest that long bones under chronic LDR-IR stress may exhibit an adaptive response to stresses such as chronic inflammation associated with IR-induced lifespan shortening. © 2022 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
电离辐射（IR）是一种众所周知的致癌物。高剂量率（HDR）IR会损害长骨（在质量和结构方面），但剂量率（特别是低剂量率[LDR]IR）、长骨状况、癌症发病率和寿命缩短之间的关系仍然不明确。本研究的目的是通过比较小鼠接受HDR-IR和LDR-IR照射的长期后果，阐明LDR-IR对长骨状况的影响。我们利用相似年龄（平均77 - 96周）的长骨的微计算机断层扫描（μCT）来比较从4周龄开始接受大致等量总剂量的内部LDR-IR或外部HDR-IR照射的小鼠及其各自的对照组。在这些混合性别的队列中，LDR-IR和HDR-IR的寿命缩短效应相似。值得注意的是，与HDR-IR小鼠相比，内部接受慢性LDR-IR照射且持续造血功能低下的小鼠显示出明显更高的小梁骨结缔组织密度[股骨：247%（P = 0.0042），胫骨：169%（P = 0.0005）]以及骨干皮质骨厚度/面积（股骨：130%[P = 0.0079]/120%[P = 0.021]，胫骨：148%[P = 0.0004]/129%[P = 0.002]）。与此结果一致，在比较IR后26 - 32周与IR后2 - 8周时，与接受HDR-IR治疗的小鼠相比，接受LDR-IR治疗的小鼠尽管炎症标志物（CCL2和CXCL1）水平显著更高（HDR-IR组P = 0.36 - 0.8，LDR-IR组P = 0.013 - 0.041），但成骨细胞标志物（OPG）水平更高（HDR-IR组P = 0.67，LDR-IR组P = 0.068），破骨细胞标志物（CTX-I）水平更低（HDR-IR组P = 0.0079，LDR-IR组P = 0.72）。这些结果表明，处于慢性LDR-IR应激下的长骨可能会对诸如与IR诱导的寿命缩短相关的慢性炎症等应激表现出适应性反应。© 2022作者。由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版。
