Elucidation of pathogenic mechanism of internal radiation-induced thyroid cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K00548
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Nagasaki University
• Principal Investigator: KURASHIGE Tomomi 長崎大学, 原爆後障害医療研究所, 助教 (60568955)
• Co-Investigator(Kenkyū-buntansha): 永山 雄二 長崎大学, 原爆後障害医療研究所, 教授 (30274632)
• Research Collaborator: SHIMAMURA Mika
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 放射線 / 甲状腺 / ROS / 発がん / オートファジー / DNA損傷

Outline of Final Research Achievements

To investigate the relationship between radiation-induced thyroid carcinogenesis and ROS, thyroid-specific autophagy deficient mice (Atg5-f/f;TPO-Cre mice), which were thought to sustainably produce much more ROS in the thyroid, were used. Atg5-f/f;TPO-Cre mice lack autophagy in a thyroid-specific manner from the embryonic stage. In the 12-months of age, accumulation of denatured protein was observed in the thyroid follicular epithelial cells of Atg5-f/f;TPO-Cre mice as compared with the control. In addition, oxidative damage (8-OHdG) and DNA double strand breaks (53BP1 foci) were also increased, which are thought to be caused by ROS from remaining undegraded defective mitochondria. These results demonstrated the relationship between sustained production of ROS and DNA damage in vivo.

Free Research Field

内分泌学

Academic Significance and Societal Importance of the Research Achievements

我々は以前、甲状腺外部被ばくの際には被ばく時だけでなく被ばく後にも持続的で高いROS産生が起こり、この被ばく後のROSによりDNA損傷が誘発され一部が修復されず染色体の異常として残ることを明らかにした。
オートファジーの不全はROS産生を恒常的に亢進させDNA損傷を増加させることから、がんの形成や進展を加速させる可能性がある。今後、甲状腺特異的にオートファジー不全を起こしたマウスに放射線照射を行い甲状腺を経時的に解析することで細胞内のROS産生の増加が甲状腺の発がんに関与するかを解明することができる。さらにROSの関与が明らかになれば抗酸化剤の投与により放射線発がんを予防できる可能性がある。