Fujimoto Nariaki, Matsuu-Matsuyama Mutsumi, Nakashima Masahiro
Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852-8523, Japan.
Int J Mol Sci. 2025 Feb 21;26(5):1874. doi: 10.3390/ijms26051874.
Childhood radiation is a risk factor for thyroid cancer that became well known after the Chernobyl nuclear plant accident. Although these human cases have been extensively studied, the mechanisms underlying childhood susceptibility to radiation-induced thyroid cancer have yet to be explained. Our previous study showed that neonatal X-irradiation resulted in long-term alterations in the mRNA expression of thyroid cancer-related marker genes, which may be a critical mechanism for understanding the higher radiation sensitivity in young patients. In this study, RNA sequencing (RNA-Seq)-based gene expression analysis was employed to identify thyroid genes whose mRNA expression was changed by neonatal irradiation. Male Wistar rats aged 1 week and 4 months were subjected to cervical X-irradiation at 4 Gy. After 8 weeks, total RNA was extracted from the thyroid and subjected to RNA-Seq analysis to identify differentially expressed genes following irradiation. We identified five upregulated genes (i.e., , , , , and ) and one downregulated gene (i.e., ) explicitly altered by neonatal radiation exposure. Western blotting confirmed the corresponding changes in CPA4 and CRTAC1 expression. The gene expressions identified were also altered in thyroid tumors induced by an iodine-deficient diet. These long-term changes in thyroid gene expression caused by neonatal irradiation may be involved in the increased risk of thyroid carcinogenesis.
儿童期辐射是甲状腺癌的一个风险因素，在切尔诺贝利核电站事故后这一点广为人知。尽管对这些人类病例已进行了广泛研究，但儿童期易患辐射诱发甲状腺癌的潜在机制仍有待阐明。我们之前的研究表明，新生儿X射线照射导致甲状腺癌相关标记基因的mRNA表达发生长期改变，这可能是理解年轻患者对辐射更高敏感性的关键机制。在本研究中，采用基于RNA测序（RNA-Seq）的基因表达分析来鉴定其mRNA表达因新生儿照射而改变的甲状腺基因。对1周龄和4月龄的雄性Wistar大鼠进行4 Gy的颈部X射线照射。8周后，从甲状腺中提取总RNA，并进行RNA-Seq分析以鉴定照射后差异表达的基因。我们鉴定出5个因新生儿辐射暴露而明显上调的基因（即 、 、 、 和 ）和1个下调基因（即 ）。蛋白质免疫印迹法证实了CPA4和CRTAC1表达的相应变化。在缺碘饮食诱导的甲状腺肿瘤中，所鉴定的基因表达也发生了改变。新生儿照射引起的甲状腺基因表达的这些长期变化可能与甲状腺癌发生风险增加有关。
