| Project/Area Number |
17K00554
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | Nagasaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中島 正洋 長崎大学, 原爆後障害医療研究所, 教授 (50284683)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | Ｘ線 / ラット / 甲状腺 / 発癌 / オートファジー / 増殖細胞 / 発がん / X線 |
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| Outline of Final Research Achievements |
To investigate the involvement of autophagy (AP) in radiation-induced thyroid cancer, hydroxychloroquine (HCQ) 200 mg / kg or saline was orally administered to 6-week-old male Wistar rats for 3 days before irradiation, and after 4 Gy whole body / local irradiation or non-irradiation, the acute radiation response of the thyroid gland and the tumor incidence in the chronic phase were investigated by dividing it into a non-irradiated non-treatment group, a non-irradiated HCQ group, a irradiated non-treatment group and a irradiated HCQ group. In the acute phase, a decrease in the number of proliferating cells and a decrease in AP-related genes were observed. Thyroid tumors were 14/15 (93.3%) in the untreated irradiated group, 9/13 (69.2%) in the HCQ group, and they were low in the HCQ group (p = 0.097). It is suggested that HCQ pretreatment may be suppressed tumor development, but further studies are needed.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでに、放射線被曝甲状腺の急性期応答として、若齢ラットでは高齡ラットと比べオートファジー関連分子の発現が促進するが、照射後慢性期の発癌時期では一部のオートファジー構成因子の遺伝子発現が低下することを見出している。「若年被曝ではオートファジーにより濾胞上皮細胞の生存に作用し、加齢とともにオートファジーの機能が抑制され、被曝細胞のうち細胞死に陥らない細胞が腫瘍化する」という仮説を検証する。甲状腺発癌早期からの動物モデルでのオートファジー機能研究はこれまでになく独創的で、若年被曝の甲状腺発癌リスク亢進の分子機構の解明に寄与する目的として、有意義なテーマとなる。
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