氟脱氧尿嘧啶致小鼠畸形。畸形早期阶段的研究。

F. Bro-Rasmussen, B. Jensen, O. Hansen, A. Ostergaard
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引用次数: 4

摘要

采用氟脱氧尿苷(FUDR)治疗不同妊娠期的104只小鼠。34只怀孕小鼠作为对照。实验小鼠在注射FUDR后每隔一段时间进行检查。足月时,幼童表现出FUDR治疗后常见的四肢和颅骨畸形。此外,度假村的数量也有所增加。妊娠第9 ~ 12天注射后24 h,畸形偏爱部位血管扩张,新鲜出血。注射后2天或更长时间取出的胎儿表现出特征性,四肢和尾部有囊状血肿,颅骨有扁平、广泛的血肿。在注射后的增加间隔,血肿的数量减少,很少出现在足月胎儿。随着血肿数量的减少,畸形数量增加。第11天给予FUDR治疗的5只小鼠,从第12天至第18天每天开腹,发现四肢血肿,并于第13天至第18天消失。电子显微镜对2个胎儿四肢的初步研究显示,注射FUDR后24小时,红细胞处于血管外状态。对照组小鼠有354个正常胎儿,自发再吸收率为8%。本研究是一项筛选实验,发现FUDR可引起血管损伤,出血并形成血肿,导致先天性畸形。血管损伤被解释为FUDR在细胞水平上的主要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Fluorodeoxyuridine-induced malformations in mice. Studies on the early stages of teratogenesis.
At different stages of gestation, 104 mice were treated with fluorodeoxyuridine (FUDR). 34 pregnant mice served as controls. The experimental mice were examined at varying intervals after the FUDR injection. At term, the young exhibited the malformations of the limbs and skull so well-known after administration of FUDR. In addition, there was an increased number of resorptions. 24 hours after the injection on the 9th—12th day of gestation, vascular dilatations and fresh haemorrhages were found at the sites of predilection of malformations. Foetuses removed 2 or more days after the injections showed characteristic, saccular haematomas in the limbs and tail as well as flat, widespread haematomas in the skull. At increasing intervals after the injections, the haematomas decreased in number and were rarely present in foetuses at term. As the number of haematomas decreased, the number of malformations increased. Daily laparotomies, from the 12th to the 18th day, on 5 mice treated on the 11th day with FUDR revealed extremity haematomas which disappeared on the 13th—18th day. Electron microscopic pilot studies of 2 foetal limbs showed, 24 hours after the injection of FUDR, red blood cells in an extra-vascular situation. The control mice had 354 normal foetuses and 8 per cent spontaneous resorptions. This study, which was a screening experiment, showed that FUDR induces vascular injury with haemorrhages and formation of haematomas, resulting in congenital malformations. The vascular injuries are interpreted as the primary action of FUDR on the cellular level.
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