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3-羟基正缬氨酸对鸡和小鼠胚胎的致畸性。

Teratogenicity of 3-hydroxynorvaline in chicken and mouse embryos.

作者信息

Louw R, Potgieter H C, Vorster W

机构信息

Division of Biochemistry, School for Chemistry and Biochemistry, Faculty of Science, North-West University, Potchefstroom, South Africa.

出版信息

Amino Acids. 2005 Nov;29(3):207-12. doi: 10.1007/s00726-005-0233-6. Epub 2005 Aug 8.

DOI:10.1007/s00726-005-0233-6
PMID:16082502
Abstract

3-Hydroxynorvaline (HNV; 2-amino-3-hydroxypentanoic acid), a microbial L-threonine analogue, is toxic to mammalian cells and displays antiviral properties. In view of this, we investigated the toxicity and/or potential teratogenicity of HNV in developing chicken and mouse embryos. HNV was administered to chicken embryos (in ovo; dose 75-300 mumole/egg; 48 h post-incubation) and pregnant Hanover NMRI mice (per os; total dose 900-1800 mg/kg body mass; gestation days 7-9). Control animals received sterile saline solutions. Harvested embryos (chicken embryos, 10 days post-incubation; mouse embryos; gestation day 18) were fixed in glutaraldehyde and stereomicroscopically inspected for signs of dysmorphogenesis. Body mass, body and toe length and mortality of chicken embryos, and the body mass and mortality of mouse embryos were recorded. HNV exposure significantly increased the incidence of embryotoxic (growth retardation, toxic mortality) and congenital defects in both chicken and mouse embryos. All the observed effects were dose-dependent. In conclusion, HNV is an embryotoxic and teratogenic compound, which caused significant developmental delay and congenital defects in developing chicken and mouse embryos.

摘要

3-羟基正缬氨酸(HNV;2-氨基-3-羟基戊酸)是一种微生物L-苏氨酸类似物,对哺乳动物细胞有毒性并具有抗病毒特性。鉴于此,我们研究了HNV对发育中的鸡和小鼠胚胎的毒性和/或潜在致畸性。将HNV施用于鸡胚(卵内注射;剂量为75-300微摩尔/蛋;孵化后48小时)和怀孕的汉诺威NMRI小鼠(经口给药;总剂量为900-1800毫克/千克体重;妊娠第7-9天)。对照动物接受无菌盐溶液。收获的胚胎(孵化后10天的鸡胚;小鼠胚胎;妊娠第18天)用戊二醛固定,并通过体视显微镜检查是否有畸形发生的迹象。记录鸡胚的体重、体长和趾长以及死亡率,以及小鼠胚胎的体重和死亡率。HNV暴露显著增加了鸡和小鼠胚胎中胚胎毒性(生长迟缓、毒性死亡)和先天性缺陷的发生率。所有观察到的效应均呈剂量依赖性。总之,HNV是一种胚胎毒性和致畸性化合物,可导致发育中的鸡和小鼠胚胎出现明显的发育延迟和先天性缺陷。

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引用本文的文献

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Threonine appears to be essential for proliferation of human as well as mouse embryonic stem cells.苏氨酸似乎对人类和小鼠胚胎干细胞的增殖至关重要。
Front Cell Dev Biol. 2014 May 20;2:18. doi: 10.3389/fcell.2014.00018. eCollection 2014.
2
Fidelity escape by the unnatural amino acid β-hydroxynorvaline: an efficient substrate for Escherichia coli threonyl-tRNA synthetase with toxic effects on growth.β-羟基正缬氨酸的非天然氨基酸的忠实逃逸:大肠杆菌苏氨酸 tRNA 合成酶的有效底物,对生长有毒性作用。
Biochemistry. 2011 Feb 15;50(6):1101-9. doi: 10.1021/bi101360a. Epub 2011 Jan 24.