COMMON HIERARCHIES OF SUSCEPTIBILITY TO THE INDUCTION OF NEURAL-TUBE DEFECTS IN MOUSE EMBRYOS BY VALPROIC ACID AND ITS 4-PROPYL-4-PENTENOIC ACID METABOLITE
COMMON HIERARCHIES OF SUSCEPTIBILITY TO THE INDUCTION OF NEURAL-TUBE DEFECTS IN MOUSE EMBRYOS BY VALPROIC ACID AND ITS 4-PROPYL-4-PENTENOIC ACID METABOLITE
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DOI：
10.1002/tera.1420380403
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发表时间：
1988-10-01
期刊：
影响因子：
--
通讯作者：
MOHL, VK
中科院分区：
文献类型：
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作者：
FINNELL, RH;BENNETT, GD;MOHL, VK
在已知对热诱导神经管缺陷具有不同敏感性的三种近交系小鼠中研究了丙戊酸及其4-丙基-4-戊烯酸（4-en）代谢产物的致畸作用。在耐热DBA/2 J菌株中，在神经管发育的关键时期给予丙戊酸或其代谢产物均未产生任何异常后代。在中度热敏感的LM/Bc品系中进行类似处理导致高达19.8%的露脑胎仔。高度热敏感的SWV菌株也非常容易受到丙戊酸或其4-烯代谢产物诱导神经管缺陷的影响。当在妊娠第8天加12小时给药时，母体化合物产生35%的露脑胎儿，而代谢产物的反应频率为32.4%。因此，在这些近交系小鼠品系中诱导神经管缺陷的易感性的层次结构是完全相同的，无论致畸剂是物理剂如高热还是化学化合物如丙戊酸。如果这些不同的因素相互作用产生畸形，那么很可能各种各样的其他因素可能以类似的方式相互作用产生神经管缺陷。
The teratogenic effects of valproic acid and its 4-propyl-4-pentenoic acid (4-en) metabolite were investigated in three inbred mouse strains that were known to possess differing sensitivity to heat-induced neural tube defects. In the heat-resistant DBA/2J strain, administration of either valproic acid or the metabolite during the critical period of neural tube development failed to produce any abnormal offspring. Similar treatment in the moderately heat-sensitive LM/Bc strain resulted in up to 19.8% exencephalic fetuses. The highly heat-sensitive SWV strain was also very susceptible to the induction of neural tube defects by either valproic acid or its 4-en metabolite. When administered on gestational day 8 plus 12 hours, the parent compound produced 35% exencephalic fetuses, while the metabolite had a response frequency of 32.4%. Thus, the hierarchy of susceptibility for the induction of neural tube defects in these inbred mouse strains was exactly the same whether the teratogen was a physical agent such as hyperthermia or a chemical compound such as valproic acid. If such diverse agents as these should interact to produce malformations, then it is possible that a wide variety of other agents might interact in a similar manner to produce neural tube defects.