Kynurenine formamidase inhibition as a possible mechanism for certain teratogenic effects of organophosphorus and methylcarbamate insecticides in chicken embryos.
Kynurenine formamidase inhibition as a possible mechanism for certain teratogenic effects of organophosphorus and methylcarbamate insecticides in chicken embryos.
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犬尿氨酸甲酰胺酶抑制是有机磷和氨基甲酸甲酯杀虫剂对鸡胚产生某些致畸作用的可能机制。
DOI：
10.1016/0006-2952(77)90288-x
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发表时间：
1977
影响因子：
5.8
通讯作者：
J. Casida
中科院分区：
文献类型：
--
作者：
A.David Moscioni;J. L. Engel;J. Casida
某些有机磷(OP)和氨基甲酸甲酯(MC)杀虫剂至少会引起两种类型的鸡胚发育异常。其中一种(I型)会导致小便和羽毛异常，另一种(II型)会导致关节僵硬、颈部扭曲和腰部无力。II型致畸与胚胎NAD水平降低有关，通过给予色氨酸到NAD生物合成途径中的中间体来恢复NAD水平，可以减轻II型致畸作用。这些和其他对鸡胚的观察表明，色氨酸向NAD转化的障碍，可能是通过抑制犬尿氨酸甲酰胺酶，导致I型畸形，但本身并不能确定。支持这一假设的是，小鼠肝脏犬尿氨酸甲酰胺酶对OP和MC化合物的体内抑制非常敏感，OP和MC化合物是鸡胚胎中最有效的NAD降低剂和致畸剂，即巴豆酰胺磷酸盐和嘧啶基硫代磷酸盐(如敌敌畏和二氮磷)以及MC化合物(如西维因)。犬尿氨酸甲酰胺酶抑制的畸胎学或其他毒理学表现可能仅限于某些物种和发育阶段，在这些阶段，酶活性降低会显著损害正常水平的NAD或由犬尿氨酸衍生的其他基本生物化学物质的维持。
At least two types of developmental anomalies are induced in chicken embryos by certain organophosphorus (OP) and methylcarbamate (MC) insecticides. One of them (TypeI) leads to micromelia and abnormal feathering and another (TypeII) involves arthrogryposis, wry neck and rumplessness. TypeIbut not typeIIteratogenesis is associated with a lowered embryo NAD level and is alleviated on restoring the NAD level by administration of intermediates in the tryptophan to NAD biosynthetic pathway. These and other observations with chicken embryos suggest but do not in themselves establish that impairment in the conversion of tryptophan to NAD, possibly by inhibition of kynurenine formamidase, leads to type I teratogenesis. This hypothesis is supported by finding that mouse liver kynurenine formamidase is extremely sensitive toin vivoinhibition by those OP and MC compounds which are the most potent NAD lowering agents and teratogens in the chicken embryo,i.e.crotonamide phosphates and pyrimidyl phosphorothionates such as dicrotophos and diazinon and MC compounds such as carbaryl. Teratological or other toxicological manifestations of kynurenine formamidase inhibition are probably restricted to species and developmental stages where reduced enzyme activity significantly impairs maintenance of normal levels of NAD or other essential biochemicals derived from kynurenine.