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猫中羟基脲和苯妥英的致畸性研究。

A teratogenicity study on hydroxyurea and diphenylhydantoin in cats.

作者信息

Khera K S

出版信息

Teratology. 1979 Dec;20(3):447-52. doi: 10.1002/tera.1420200314.

Abstract

Hydroxyurea, an antitumor drug and known teratogen in rat, miniature swine and dog, and diphenylhydantoin, a teratogen in mouse and rat, were assessed for teratogenic effects in cat. Pregnancies were induced, by synchronizing gonadotropin-stimulated estrus and ovulation with natural copulations. Hydroxyurea at 50 or 100 mg/kg, and sodium diphenylhydantoin at 1 or 2 mg/kg dosages, were administered orally in single daily doses from gestation days 10-22. Appropriate controls given empty capsules, were included for each drug. Cats were necropsied on gestation day 43. Fetuses were examined for external, visceral and skeletal malformations. Hydroxyurea at 50 mg/kg dose produced a low teratogenic activity and at 100 mg/kg a high incidence of non-pregnancy and resorptions with, consequently, fewer live fetuses. Diphenylhydantoin gave no clear evidence of teratogenicity at any test dose but was embryolethal at the maternally toxic dose of 2 mg/kg. So far, studies conducted suggest that the cat is a useful species for screening drugs and chemicals for their teratogenic potential.

摘要

羟基脲是一种抗肿瘤药物,在大鼠、小型猪和狗中是已知的致畸剂,苯妥英在小鼠和大鼠中是致畸剂,对其在猫中的致畸作用进行了评估。通过促性腺激素刺激的发情和排卵与自然交配同步诱导怀孕。在妊娠第10至22天,每天口服50或100mg/kg的羟基脲,以及1或2mg/kg剂量的苯妥英钠,每日单剂量给药。每种药物均设置给予空胶囊的适当对照组。在妊娠第43天对猫进行尸检。检查胎儿的外部、内脏和骨骼畸形。50mg/kg剂量的羟基脲产生低致畸活性,100mg/kg剂量时非妊娠和吸收的发生率很高,因此活胎较少。苯妥英在任何测试剂量下均未显示出明确的致畸证据,但在2mg/kg的母体毒性剂量下具有胚胎致死性。到目前为止,进行的研究表明,猫是筛选药物和化学物质致畸潜力的有用物种。

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