Department of Integrated Biosciences, The University of Tokyo, Kashiwa, Japan.
Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology (QST), National Institute of Radiological Sciences, Chiba, Japan.
Int J Radiat Biol. 2023;99(4):663-672. doi: 10.1080/09553002.2022.2110328. Epub 2022 Aug 19.
Hematopoietic tissues of vertebrates are highly radiation sensitive and the effects of ionizing radiation on the hematopoiesis have been studied in mammals and teleosts for decades. In this study, radiation responses in the kidney, the main hematopoietic organ in teleosts, were investigated in Japanese medaka (), which has been a model animal and a large body of knowledge has been accumulated in radiation biology.
Kidney, the main hematopoietic tissue of adult medaka fish, was locally irradiated using proton and carbon ion beams irradiation system of Takasaki Ion Accelerator for Advanced Radiation Application (TIARA), QST, and the effects on peripheral blood cells and histology of the kidney were investigated.
When only kidneys were locally irradiated with proton or carbon ion beam (15 Gy), the hematopoietic cells in the irradiated kidney and cell density in the peripheral blood decreased 7 days after the irradiation in the same manner as after the whole-body irradiation with γ-rays (15 Gy). These results demonstrate that direct irradiation of the hematopoietic cells in the kidney induced cell death and/or cell cycle arrest and stopped the supply of erythroid cells. Then, the cell density in the peripheral blood recovered to the control level within 4 days and 7 days after the γ-ray and proton beam irradiation (15 Gy), respectively, while the cell density in the peripheral blood did not recover after the carbon ion beam irradiation (15 Gy). The hematopoietic cells in the irradiated kidneys temporarily decreased and recovered to the control level within 21 days after the γ-ray or proton beam irradiation (15 Gy), while it did not recover after the carbon ion beam irradiation (15 Gy). In contrast, the recovery of the cell density in the peripheral blood delayed when anemic medaka were irradiated 1 day after the administration of phenylhydrazine. With and without γ-ray irradiation, a large number of hematopoietic cells was still proliferating in the kidney 7 days after the anemia induction.
The results obtained strongly suggest that the hematopoietic stem cells in medaka kidney prioritize to proliferate and increase peripheral blood cells to eliminate anemia, even when they are damaged by high-dose irradiation.
脊椎动物的造血组织对电离辐射极为敏感,几十年来,人们一直在哺乳动物和硬骨鱼中研究电离辐射对造血的影响。在这项研究中,我们研究了日本青鳉()肾脏中的辐射反应,肾脏是硬骨鱼的主要造血器官,日本青鳉已经成为一种模式动物,并且在辐射生物学方面积累了大量的知识。
使用高崎尖端医科学研究产业财团的 Takasaki Ion Accelerator for Advanced Radiation Application (TIARA)质子和碳离子束辐照系统对成年青鳉鱼的肾脏(主要造血组织)进行局部辐照,并研究了对外周血细胞和肾脏组织学的影响。
当仅用质子或碳离子束(15Gy)对肾脏进行局部照射时,与全身γ射线(15Gy)照射后一样,照射后 7 天,受照射肾脏中的造血细胞和外周血中的细胞密度均下降。这些结果表明,直接辐照肾脏中的造血细胞会诱导细胞死亡和/或细胞周期停滞,并停止红细胞的供应。然后,在γ射线和质子束照射(15Gy)后,外周血中的细胞密度分别在 4 天和 7 天内恢复到对照水平,而在碳离子束照射(15Gy)后则没有恢复。受照射肾脏中的造血细胞暂时减少,并在γ射线或质子束照射(15Gy)后 21 天内恢复到对照水平,而在碳离子束照射(15Gy)后则没有恢复。相比之下,在苯肼给药后 1 天贫血的青鳉鱼照射时,外周血中细胞密度的恢复会延迟。无论是否进行γ射线照射,在贫血诱导后 7 天,仍有大量造血细胞在肾脏中增殖。
这些结果强烈表明,即使造血干细胞受到高剂量辐射的损伤,日本青鳉肾脏中的造血干细胞仍会优先增殖并增加外周血细胞以消除贫血。