5-Fluorouracil (5-Fu) is a DNA-damaging agent and teratogenic in rodents. This study aimed to investigate its influence on neural progenitor cells (NPCs) in the developing fetal rat brain. Dams were intraperitoneally injected with 5-Fu (50 mg/kg b.w.) on gestation day 13 and its effects on fetal NPCs were observed from 3 to 72 hours after treatment (HAT), via periodic examination at six intervals. In NPCs of the fetal brain, the p53-labeling index (LI%) was markedly elevated at 3 HAT. Pyknosis and cleaved caspase-3-LI% also increased at 3 HAT, reaching peak values at 9 and 12 HAT. These parallel changes suggested the induction of apoptosis through a p53-mediated pathway. Pyknotic NPCs were distributed across the ventricular zone (VZ) of the telencephalic wall until 12 HAT, and became localized in the medial and dorsal layers at 12 and 48 HAT. Significant decreases in the numbers of mitotic NPCs and BrdU-LI% were noted from 3 HAT and 24 HAT, respectively. BrdU-positive NPCs were located in the ventral and middle layer at 24 and 48 HAT. p21-positive cells were detected at 12 and 24 HAT. The present results demonstrated that p53-mediated apoptosis was induced in all phases of the cell cycle of the NPCs in the early stage after 5-FU treatment. Furthermore, apoptosis of NPCs and suppression of cell proliferative activity are the events that take place in parallel leading to prominent reduction in the width of the telencephalic wall.
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机译：5-氟尿嘧啶 （5-Fu） 是一种 DNA 损伤剂，在啮齿动物中具有致畸作用。本研究旨在探讨其对发育中的胎鼠大脑中神经祖细胞 （NPCs） 的影响。妊娠第 13 天腹膜内注射 5-Fu （50 mg/kg b.w.），治疗后 3 至 72 小时 （HAT） 观察其对胎儿 NPC 的影响，间隔 6 次定期检查。在胎脑的 NPC 中，p53 标记指数 （LI%） 在 3 HAT 时显著升高。Pyknosis 和裂解的 caspase-3-LI% 在 3 HAT 时也增加，在 9 和 12 HAT 处达到峰值。这些平行变化表明通过 p53 介导的通路诱导细胞凋亡。Pyknotic NPC 分布在端脑壁的心室区 （VZ） 直到 12 HAT，并在 12 和 48 HAT 时定位于内侧和背层。分别从 3 HAT 和 24 HAT 开始观察到有丝分裂 NPC 和 BrdU-LI% 的数量显着减少。BrdU 阳性 NPC 位于 24 和 48 HAT 的腹侧和中间层。在 12 和 24 HAT 检测到 p21 阳性细胞。目前的结果表明，在 5-FU 处理后，p53 介导的细胞凋亡在 NPCs 细胞周期的早期所有阶段均被诱导。此外，NPC 的凋亡和细胞增殖活性的抑制是同时发生的事件，导致端脑壁的宽度显着减小。
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