The in vitro teratogenicity of cyclophosphamide in rat embryos.
The in vitro teratogenicity of cyclophosphamide in rat embryos.
复制标题
环磷酰胺对大鼠胚胎的体外致畸性。
DOI：
10.1002/tera.1420250310
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Juchau,MR
中科院分区：
文献类型：
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作者：
Greenaway,JC;Fantel,AG;Shepard,TH;Juchau,MR
当第10天的大鼠胚胎在含有环磷酰胺、肝微粒体组分(S-9)和单氧辅因子的培养中生长时，它们会出现特征性的畸形。在培养液中加入一定体积的CP后，畸形胚数增加，畸形胚数减少，且与S-9浓度呈正相关。在一组实验中，S-9是从用苯巴比妥(PB)或3-甲基胆蒽(MCA)预处理的动物中制备的。用多氯联苯(Aroclor1254)(μL/ml)处理的动物，用S-9的CP培养的所有胚胎。用大脑中动脉诱导的S-9(0.2 5~12.5μL/ml)替代，在相同条件下未见畸形。经多氯联苯(Aroclor1254)处理的动物，S-9对CP的致畸活性在体外可被添加甲替拉酮或一氧化碳抑制。第10天，体内暴露于CP(25 mg/kg)的胚胎与体外处理的胚胎没有区别。与只接受车辆的对照窝仔相比，所有的仔猪都出现了特征缺陷，并且生长参数显著降低。在体内和体外处理的胚胎之间没有组织学上的差异。这些数据进一步证明，CP的致畸作用依赖于一个或多个母体P450单加氧酶系统。
When Day 10 rat embryos were grown in culture containing cyclophosphamide, an hepatic microsomal fraction (S‐9), and cofactors for monooxygenation, they developed characteristic malformations. When a fixed volume of CP was added to cultures the number of malformed embryos was increased and their growth decreased dependent upon the S‐9 concentration. In one group of experiments S‐9 was prepared from animals which had been pretreated with either phenobarbital (PB) or 3‐methylcholanthrene (MCA). All embryos cultured with CP by S‐9 from animals pretreated with polychlorinated biphenyls (Aroclor 1254) (μl/ml) was used. No malformations were seen under the same conditions when MCA‐induced S‐9 (0.25–12.5 μl/ml) was substituted. The teratogenic activation of CP by S‐9 from animals pretreated with polychlorinated byphenyls (Aroclor 1254) was inhibited in vitro by the addition of either metyrapone or carbon monoxide. Embryos which were exposed to CP (25 mg/kg) in vivo on Day 10 were indistinguishable from embryos treated in vitro. All developed characteristic defects and had significant decreases in growth parameters when compared to control litters receiving only vehicle. No histological differences were seen between embryos treated in vivo or in vitro. These data provide further evidence that the teratogenicity of CP is dependent upon one or more maternal P450 monooxygenase systems.