MORPHOLOGICAL DIFFERENCES ELICITED BY 2 WEAK ACIDS, RETINOIC AND VALPROIC, IN RAT EMBRYOS GROWN-INVITRO
MORPHOLOGICAL DIFFERENCES ELICITED BY 2 WEAK ACIDS, RETINOIC AND VALPROIC, IN RAT EMBRYOS GROWN-INVITRO
复制标题
DOI：
10.1002/tera.1420430206
复制
发表时间：
1991-02-01
期刊：
影响因子：
--
通讯作者：
JUCHAU, MR
中科院分区：
文献类型：
--
作者：
SEEGMILLER, RE;HARRIS, C;JUCHAU, MR
我们比较了丙戊酸（VPA）和反式维甲酸（RA）在大鼠全胚培养中引起的形态学变化。在妊娠第9.5天外植的大鼠胚胎在第10天用浓度相等的RA或VPA处理胚胎蛋白。通过扫描和透射电镜形态学评估所选择的浓度，RA和VPA分别为2.3和800 μ m，在培养系统的初始范围寻找实验中产生了大约50%的前神经孔异常打开的发生率。在三种不同的剂量下，对相应组的胚胎进行蛋白质和DNA分析。以并发对照组为参照标准，比较两处理组的内外形态、蛋白质和DNA含量、生长指标的差异。虽然某些变量在两个治疗组中反应相似，例如生长变量、蛋白质和DNA含量，但每种药物都产生选择性形态效应。而类风湿关节炎治疗导致鳃弓发育不全，对称裂颅缺陷导致脑前侧和脑前侧区域开口，尾侧神经孔区域神经组织外化，VPA导致神经管全长不规则裂，边缘呈波浪状，尾侧神经孔开放，神经上皮未外翻，但对鳃弓没有可检测到的影响。这两种药物对蛋白质和DNA含量的相似影响表明其总体毒性程度相当；然而，对神经管和鳃弓的不同作用，加上产生这种作用所需药物浓度的巨大差异，增加了它们引发异常发育的机制有质的不同的证据。
We compared in rat whole-embryo culture the morphological changes elicited by valproic acid (VPA) with those elicited by trans-retinoic acid (RA). Rat embryos explanted on day 9.5 of gestation were treated on day 10 with RA or VPA at concentrations producing equivalent reductions in embryonic protein. The concentrations selected for morphological assessment by scanning and transmission electron microscopy, 2.3 and 800-mu-M, respectively, for RA and VPA, produced approximately a 50% incidence of abnormally open anterior neuropores in initial range-finding experiments in the culture system. Protein and DNA analyses were also performed on corresponding groups of embryos at three different doses. With concurrent control groups used as reference standards, the two treatment groups were compared for differences in external and internal morphology, protein and DNA contents, and growth indices. While certain variables responded similarly in the two treatment groups, e.g., the growth variables, protein and DNA contents, each drug produced selective morphological effects. Whereas treatment with RA produced underdeveloped branchial arches, symmetrically cleft cranial defects resulting in openings in rhombencephalic and prosencephalic regions, and exteriorized neural tissue in the caudal neuropore region, VPA produced irregular clefts with wavy margins along the entire length of the neural tube, and an open caudal neuropore without eversion of the neuroepithelium, while producing no detectable effect on the branchial arches. The similar effects of these two drugs on protein and DNA contents suggest comparable degrees of overall toxicity; however, the dissimilar effects on neural tube and branchial arches, coupled with the large difference in concentration of the drug required to produce the effects, add to the evidence that their mechanisms for elicitation of abnormal development are qualitatively different.