Ethanol teratogenicity in mice: a light microscopic study.
Ethanol teratogenicity in mice: a light microscopic study.
复制标题
乙醇对小鼠的致畸性：光学显微镜研究。
DOI：
10.1002/tera.1420260305
复制
发表时间：
1982
期刊：
影响因子：
--
通讯作者：
P. Burke
中科院分区：
文献类型：
--
作者：
J. Bannigan;P. Burke
本研究的目的是观察在妊娠第9天单次注射乙醇（一种已知的人类和动物致畸剂）后小鼠胚胎中发生的细胞变化（如果有的话）。直到注射后6小时才观察到变化，此时在神经沟和神经管的神经上皮中观察到许多变性细胞和坏死碎片。此外，许多细胞的细胞质中可见大的透明空泡，神经沟腔侧的伪足出现肿胀。后者的细胞质也含有空泡。当氚标记的胸苷注射后5小时乙醇和1小时前处死，许多退化的细胞被标记。此外，许多细胞核标记的细胞质中有异常空泡。因此，乙醇的毒性可能主要作用于细胞质的某些组分，而不是DNA合成。乙醇后12小时，细胞质空泡和肿胀的伪足消失，但死亡细胞仍然明显。到24小时，坏死碎片已被健康的神经上皮细胞完全吞噬。到50小时，神经上皮细胞碎片已被清除，尽管许多乙醇处理的胚胎有颅神经管的开放性缺陷。用单剂量乙醛（也是动物中确定的致畸剂）治疗妊娠小鼠，未产生任何细胞变化。然而，单剂量的乙醛被母亲迅速代谢，并且不能与一剂量的乙醇产生的小但连续的血液水平相比。因此，我们不能肯定地得出结论，乙醇的细胞毒性作用是直接发挥的。
The objective of this study was to see what, if any, cellular changes occurred in the mouse embryo following a single injection of ethanol, a known teratogen in humans and animals, on day 9 of gestation. No changes were seen until 6 hours after injection, when many degenerating cells and necrotic fragments were seen in the neuroepithelium of the neural groove and of the neural tube. In addition, large clear vacuoles were seen in the cytoplasm of many cells and the pseudopodia at the luminal side of the neural groove appeared swollen. The cytoplasm of the latter also contained vacuoles. When tritiated thymidine was injected 5 hours after ethanol and 1 hour before sacrifice, many degenerating cells were labelled. In addition, many cells with labelled nuclei had abnormal vacuoles in the cytoplasm. Hence, it is likely that the toxicity of ethanol is exerted primarily on some component of the cytoplasm and not on DNA synthesis. Twelve hours after ethanol, the cytoplasmic vacuoles and swollen pseudopodia had disappeared, but dying cells were still evident. By 24 hours, the necrotic debris had been completely phagocytosed by healthy neuroepithelial cells. By 50 hours, the neuroepithelium had been cleared of cell debris, although many ethanol-treated embryos had open defects of the cranial neural tube. Treatment of pregnant mice with single doses of acetaldehyde, also an established teratogen in animals, did not produce any cellular changes. However, a single dose of acetaldehyde is rapidly metabolized by the mother, and would not be comparable to the small but continuous blood levels that a dose of ethanol would produce. Hence, we could not conclude with certainty that the cytotoxic effects of ethanol were exerted directly.