Online ISSN: 1884-4111 Print ISSN: 0033-8303
Radioisotopes 68(3): 105-113 (2019)


33P β線源の妊娠マウスへの投与によって起こった低線量胎内被ばく誘発小頭症Microcephaly Due to Low-dose Intrauterine Radiation Exposure Caused by 33P β Administration to Pregnant Mice

国立循環器病研究センター研究所研究安全管理室Laboratory for Occupational Safety and Health, National Cerebral and Cardiovascular Center Research Institute ◇ 565–8565 大阪府吹田市藤白台5–7–1 ◇ 5–7–1 Fujishirodai, Suita-shi, Osaka 565–8565, Japan

受付日:2018年10月10日Received: October 10, 2018
受理日:2018年11月11日Accepted: November 11, 2018
発行日:2019年3月15日Published: March 15, 2019

本実験は,器官形成期にある妊娠マウスを使って,低線量胎内被ばくの影響を,2次元電気泳動と質量分析を組み合わせた実験系から調べた。その結果,Ras GTPase-activating protein–binding protein 1とRho GDP-dissociation inhibitor 1が,3.7 MBq 33P-ATPの母親への投与により,胎児組織で著しく増加することがわかった。この時の,母親の注射部位周辺で,投与後3日間における総線量は約50 mGyであった。さらにこの生化学的変化が小頭症に関連するものかを確かめるために,PQBP1(Polyglutamine binding protein 1)発現をウエスタンブロット法で調べてみたところ,3.7 MBq投与により,胎児組織でPQBP1発現が抑制されており,低線量の内部被ばくでも小頭症が疑える変化が誘発されたことがわかった。

The effects of low-dose rate/low-dose intrauterine exposure during organogenesis were investigated using pregnant mice and an experimental system employing both 2-D electrophoresis and mass spectrometry. Ras GTPase-activating protein-binding protein 1 and Rho GDP-dissociation inhibitor 1 are known to play vital roles in the morphological development of the nervous system such as synaptic plasticity and elongation of axons. These proteins showed a marked increase in fetal tissues collected 3 days after mothers were administered 3.7 MBq 33P-ATP. This suggests that active GTPase decreases and inactive GTPase increases resulting in a disruption of neurotransmission. To confirm if these changes were associated with microcephaly, PQBP1 (Polyglutamine binding protein 1) expression was determined by Western blot assay. Administration of 3.7 MBq resulted in a marked inhibition of PQBP1 expression in fetal tissues proving that even low-dose internal exposure was enough to induce changes suggestive of microcephaly. Actual measured values from the maternal injection site confirmed that the total dose over the 3 days after administration is about 50 mGy. This demonstrates that even low-dose intrauterine exposure warrants caution, suggesting that appropriate radiation safety measures such as education pertaining to the risks of exposure is important for pregnant workers.

Key words: microcephaly; PQBP1 (Polyglutamine binding protein 1); internal exposure; low-dose exposure; CNS (central nervous system)

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