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[VP 16-213(IV)的生殖研究——围产期和哺乳期对大鼠进行口服给药]

[Reproduction studies of VP 16-213 (IV)--Oral administration to rats during the perinatal and lactation periods].

作者信息

Takahashi N, Kai S, Kohmura H, Ishikawa K, Kuroyanagi K, Hamajima Y, Ohta S, Kadota T, Kawano S, Ohta K

出版信息

J Toxicol Sci. 1986 Apr;11 Suppl 1:241-61. doi: 10.2131/jts.11.supplementi_241.

Abstract

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to female Crj: CD (Sprague-Dawley) rats from day 17 of gestation through postpartum day 20 at dose levels of 1, 3 and 10 mg/kg/day. The summarized results obtained are as follows: VP 10 mg/kg induced thymic atrophy in dams. VP failed to affect the parturition of dams. VP 10 mg/kg lowered the viability of newborns (F1) on postpartum day 3 and increased the days required for descending of testes, but failed to affect the growth of genital organs, learning ability, motility motor activity or emotional development. VP 10 mg/kg brought a transient suppression of body weight increase in pregnant F1 rats, but failed to affect their reproductive ability and parturition. F2 newborns derived from F1 rats whose dams had ever received VP during the prenatal and lactation periods showed no changes in observation items at birth. Long-term rearing F1 rats derived from VP-treated dams manifested no delayed toxicity including carcinogenicity. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 3 mg/kg/day against dams and their offspring.

摘要

依托泊苷(VP 16 - 213,简称VP)是一种抗癌药物,在妊娠第17天至产后第20天,以1、3和10毫克/千克/天的剂量水平对雌性Crj:CD(斯普拉格 - 道利)大鼠进行口服给药。获得的总结结果如下:10毫克/千克的VP导致母鼠胸腺萎缩。VP对母鼠分娩没有影响。10毫克/千克的VP降低了产后第3天新生幼崽(F1)的存活率,并延长了睾丸下降所需天数,但未影响生殖器官的生长、学习能力、运动活动或情绪发育。10毫克/千克的VP使怀孕的F1代大鼠体重增加出现短暂抑制,但未影响其生殖能力和分娩。在产前和哺乳期母鼠曾接受过VP处理的F1代大鼠所产的F2代新生幼崽,出生时观察项目无变化。对VP处理母鼠所产F1代大鼠进行长期饲养,未表现出包括致癌性在内的延迟毒性。基于这些结果,在本实验条件下,VP对母鼠及其后代的无作用剂量水平估计为3毫克/千克/天。

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