Mechanisms of chemical-induced fetal brain toxicity

化学物质引起胎儿脑毒性的机制

• 批准号: 13460139
• 负责人: DOI Kunio
• 金额: $ 9.6万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13460139/
• 关键词: apoptosis; cell cycle arrest; fetal brain; chemicals; mechanisms; ENU; A ra-C; 5AzC; NMDA; fetotoxicity; placental toxicity; ethylnitrosourea; 5-azacytidine; apotosis; Ethylnitrosourea; ラット胎仔中枢神経; ラット胎盤; アポトーシス; 細胞周期停止; rpL4; mistosis

Mechanisms of chemical-induced fetal brain toxicity were studies using the combination of 6 chemicals and mice or rats. As a result, apoptosis and cell cycle arrest were generally observed in neural epithelial cells. However, the site and sequence of apoptosis and the phase of cell cycle arrest were different among chemicals. In addition, except for T-2 toxin, apoptosis and cell cycle arrest occurred through p53-dependent pass way. In the case of T-2 toxin, apoptosis was induced by oxidative stress and subsequent mitochondrial damage. Furthermore, in the cases of ENU, Ara-C and T-2 toxin, apoptosis and cell cycle arrest were induced also in placenta through the same pass way in the fetal brain.These results are considered to be very useful for further investigation of the mechanisms of fetotoxicity.

本文用6种化学品联合应用于小鼠或大鼠，研究了化学品对胎脑的毒性机制。结果，在神经上皮细胞中普遍观察到凋亡和细胞周期阻滞。但不同化学物质诱导细胞凋亡的部位、顺序和细胞周期阻滞的时相不同。除T-2毒素外，凋亡和细胞周期阻滞均通过p53依赖的途径发生。在T-2毒素的情况下，细胞凋亡诱导的氧化应激和随后的线粒体损伤。此外，ENU、Ara-C和T-2毒素也可通过胎脑中同样的途径诱导胎盘细胞凋亡和细胞周期阻滞，这些结果为进一步研究胎儿毒性的机制提供了重要依据。

项目成果

Takai H., Katayama H., Uetsuka K., Yasoshima A., Uetsuka K., Nakayama H., Doi K.: "NMDA-induced apoptosis in the developing rat brain."Experimental and Toxicologic Pathology. 55. 33-37 (2003)

Takai H.、Katayama H.、Uetsuka K.、Yasoshima A.、Uetsuka K.、Nakayama H.、Doi K.：“NMDA 诱导发育中的大鼠大脑细胞凋亡。”实验和毒理学病理学。

Ueno M.et al.: "Expression of ribosomal protein L4 (rpL4) during neurogenesis and 5-azacytidine (5AzC)-induced apoptotic process in the rat"Histology and Histopathology. Vol.17. 789-798 (2002)

Ueno M.等人：“大鼠神经发生和 5-氮杂胞苷 (5AzC) 诱导的细胞凋亡过程中核糖体蛋白 L4 (rpL4) 的表达”组织学和组织病理学。

Yamauchi H., Katayama K., Ueno M., Nakayama H., Doi K.: "Involvement of p53 in 1-β-D-arabinofuranosylcytosine-induced rat fetal brain lesion."Neurotoxicity and Teratology. (in press). (2004)

Yamauchi H.、Katayama K.、Ueno M.、Nakayama H.、Doi K.：“p53 在 1-β-D-阿拉伯呋喃糖基胞嘧啶诱导的大鼠胎儿脑损伤中的参与。”神经毒性和畸胎学（出版中）。 ）

Katayama K., Ohtsuka R., Takai H., Nakayama H., Doi: "Expression of p53 and its transcriptional target genes mRNAs in the ethylnitrosourea-induced apotosis and cell cycle arrest in the fetal central nervous system."Histology and Histopathology. 17. 715-72

Katayama K.、Ohtsuka R.、Takai H.、Nakayama H.、Doi：“p53 及其转录靶基因 mRNA 在乙基亚硝基脲诱导的胎儿中枢神经系统细胞凋亡和细胞周期停滞中的表达。”组织学和组织病理学。

Yamauchi H. et al.: "Involvement of p53 in 1-β-D-arabinofuranosylcytosine-induced irophoblastic cell apoptosis and impaired proliferation in rat placenta."Biology of Reproduction. Vol.70(In press). (2004)

Yamauchi H. 等人：“p53 参与 1-β-D-阿拉伯呋喃糖基胞嘧啶诱导的成纤维细胞凋亡和大鼠胎盘增殖受损”。《生殖生物学》第 70 卷（出版中）。