Differences in Sfpi1 gene deletion in hematopoietic cells after repeated low-dose X-ray partial irradiation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K20451
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 63020:Radiation influence-related
• Research Institution: Oita University of Nursing and Health Sciences
• Principal Investigator: Etani Reo 大分県立看護科学大学, 看護学部, 助教 (20783450)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 低線量放射線 / 造血幹細胞 / 遺伝子変異 / 繰り返し照射

Outline of Final Research Achievements

In this study, we examined the difference in frequency of hemizygous deletion of the Sfpi1 gene, an initiating event for the development of radiation-induced AML (rAML), in hematopoietic stem cells from mice irradiated with 1 Gy X-ray. 8-weeks old male C3H mice were irradiated 1Gy of total body X-ray or partially irradiated to the head.The irradiation method was single irradiation or 10 repeated irradiations of 100 mGy once at 24-hour intervals respectively. At 1, 4, 12, and 26 weeks post-irradiation, we found that the number of HSCs and the frequency of Sfpi1 gene deletion from bone marrow of the femur, bone marrow of the skull and spleen cells respectively. The results suggest that HSCs with a deletion of the Sfpi1 gene may accumulate in various hematopoietic tissues over time. In addition, the deletion of the Sfpi1 gene after irradiation increased in the single irradiation group as compared with the non-irradiated group, and was higher than that in the repeated irradiation group.

Free Research Field

放射線影響

Academic Significance and Societal Importance of the Research Achievements

CT検査のような低線量放射線の繰り返し被ばくと発がんリスクに関する詳細な情報は少ない。そこで本研究では、低線量放射線の繰り返し暴露による白血病発症のメカニズムの特徴を明らかにするため、rAMLのモデルであるC3H系マウスの全身にX線を単回照射あるいは分割で繰り返し照射し、骨髄細胞中に生成されるrAML発症に関与するSfpi1遺伝子の欠失頻度とその時間変化の差異について検討した。24時間という比較的短い照射間隔をとることや一回線量を低くすることによって、遺伝子欠失を有するHSCの細胞動態（蓄積と排除）に影響を与え、rAML発症リスクに影響することが示唆された。