Abstract
Purpose
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 (Oryzias latipes), which has been a model animal and a large body of knowledge has been accumulated in radiation biology.
Methods
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.
Results
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.
Conclusions
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.
Acknowledgments
The authors thank the crew of the cyclotron of TIARA at QST-Takasaki for their kind support for providing fine beams.
Author contributions
K.N., K.O., C.H., S.O., T.W.-A. and H.M. designed the experiments, T.F. and M.S. tuned the ion beams and evaluated the beam quality, K.N., K.O., T.K., C.H., A.H.S., T.Y., B.D., T.F., M.S., S.O. and T.W.-A. conducted the experiments, K.N., K.O., C.H., A.E.-D.H.S., S.O. and T.W.-A. analyzed the data, T.W.-A., T.F., S.O. K.N., A.H.S. and H.M. interpreted result of the experiment, K.N., T.F., S.O., T.W.-A. and H.M. drafted manuscript, K.N., T.F., M.S., S.O., T.W.-A. and H.M. edited manuscript. All authors have read and approved the final manuscript.
Disclosure statement
No potential conflict of interest was reported by the authors.
Additional information
Funding
Notes on contributors
Kento Nagata
Kento Nagata, Ph.D., is a researcher of National Institute of Radiological Sciences, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology (QST), Chiba, Japan.
Keita Ohashi
Keita Ohashi, M.Sc., was a student of Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.
Chika Hashimoto
Chika Hashimoto, M.Sc. is a medical student of Hirosaki University, School of Medicine, Hirosaki, Japan.
Alaa El-Din Hamid Sayed
Alaa El-Din Hamid Sayed, Ph.D., is a professor of Department of Zoology, Faculty of Science, Assuit University, Assuit, Egypt.
Takako Yasuda
Takako Yasuda, Ph.D., is a researcher of Department of Chemical and Biological Sciences, Japan Women’s University, Tokyo, Japan.
Bibek Dutta
Bibek Dutta, M.Sc., is a PhD, student in Cancer Science Institute of Singapore, National University of Singapore.
Takayuki Kajihara
Takayuki Kajihara, M.Sc., was a student of Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.
Hiroshi Mitani
Hiroshi Mitani, Ph.D., is an emeritus professor of Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.
Michiyo Suzuki
Michiyo Suzuki, Ph.D., is a principal researcher of Takasaki Advanced Radiation Research Institute, Quantum Beam Science Research Directorate, QST, Takasaki, Japan.
Tomoo Funayama
Tomoo Funayama, Ph.D., is the project leader of "Microbeam Radiation Biology" at Takasaki Advanced Radiation Research Institute, Quantum Beam Science Research Directorate, QST, Takasaki, Japan.
Shoji Oda
Shoji Oda, Ph.D., is an associate professor of Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.
Tomomi Watanabe-Asaka
Tomomi Watanabe-Asaka, Ph.D., is an assistant professor of Division of Physiology, Faculty of Medicine, Tohoku Medical Pharmaceutical University, Sendai, Japan.