Age at exposure is a critical factor that influences the risk of radiation-induced leukemia. Accumulating evidence suggests that ionizing radiation can induce genomic instability and promote leukemogenesis in hematopoietic stem cells (HSCs); however, the influence of age on this phenomenon has not been elucidated. In this study, infant (1-week-old) or adult (14-week-old) C3H/He mice received sham or 4 Gy whole-body irradiation, and bone marrow cells were transplanted to recipients at day 1 or 60 postirradiation. Twelve days after bone marrow transplant, we analyzed the radiation-induced genomic instability by scoring the frequency of DNA damage and micronucleus formation in colony-forming units-spleen (CFU-Ss). We observed significant increases in DNA damage and micronucleus formation in CFU-Ss of the 4 Gy irradiated adult cells transplanted at day 1 or 60 postirradiation. However, the frequency of DNA damage focus and micronucleus formation in CFU-Ss of 4 Gy irradiated infant cells transplanted at day 1 or 60 postirradiation was relatively decreased. Quantitative differences in the reactive oxygen species and cells expressing inducible nitric oxide synthase in CFU-Ss suggested that age-dependent radiation-induced genomic instability may result from chronic oxidative stress by pro-inflammatory states in HSC descendants after radiation exposure.
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1 December 2018
REGULAR ARTICLES|
October 12 2018
Age Dependence of Radiation-Induced Genomic Instability in Mouse Hematopoietic Stem Cells
Kentaro Ariyoshi;
Kentaro Ariyoshi
1
aDepartment of Radiation Biology, Institute of Radiation Emergency Medicine, Hirosaki University, 66-1 Hon-cho, Hirosaki 036-8564, Japan
1Addresses for correspondence: Hirosaki University, Institute of Radiation Emergency Medicine, 66-1 Hon-cho, Hirosaki 036-8564, Japan; email: ariyoshi@hirosaki-u.ac.jp
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Tomisato Miura;
Tomisato Miura
bDepartment of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan
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Kosuke Kasai;
Kosuke Kasai
bDepartment of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan
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Nakata Akifumi;
Nakata Akifumi
cDepartment of Basic Pharmacy, Hokkaido Pharmaceutical University School of Pharmacy, 7-1 Katsuraoka-cho, Otaru, Hokkaido 047-0264, Japan
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Yohei Fujishima;
Yohei Fujishima
bDepartment of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan
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Mayumi Shinagawa;
Mayumi Shinagawa
dDepartment of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, 263-8555, Japan
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Kyoko Kadono;
Kyoko Kadono
dDepartment of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, 263-8555, Japan
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Mayumi Nishimura;
Mayumi Nishimura
dDepartment of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, 263-8555, Japan
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Shizuko Kakinuma;
Shizuko Kakinuma
dDepartment of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, 263-8555, Japan
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Mitsuaki A. Yoshida
Mitsuaki A. Yoshida
1
aDepartment of Radiation Biology, Institute of Radiation Emergency Medicine, Hirosaki University, 66-1 Hon-cho, Hirosaki 036-8564, Japan
1Addresses for correspondence: Hirosaki University, Institute of Radiation Emergency Medicine, 66-1 Hon-cho, Hirosaki 036-8564, Japan; email: ariyoshi@hirosaki-u.ac.jp
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Radiat Res (2018) 190 (6): 623–633.
Article history
Received:
April 09 2018
Accepted:
August 29 2018
Citation
Kentaro Ariyoshi, Tomisato Miura, Kosuke Kasai, Nakata Akifumi, Yohei Fujishima, Mayumi Shinagawa, Kyoko Kadono, Mayumi Nishimura, Shizuko Kakinuma, Mitsuaki A. Yoshida; Age Dependence of Radiation-Induced Genomic Instability in Mouse Hematopoietic Stem Cells. Radiat Res 1 December 2018; 190 (6): 623–633. doi: https://doi.org/10.1667/RR15113.1
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