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斑马鱼(Danio rerio)胚胎中亚砷酸盐毒性的发育机制。

Developmental mechanisms of arsenite toxicity in zebrafish (Danio rerio) embryos.

作者信息

Li Dan, Lu Cailing, Wang Ju, Hu Wei, Cao Zongfu, Sun Daguang, Xia Hongfei, Ma Xu

机构信息

Department of Genetics, National Research Institute for Family Planning, Beijing, China.

出版信息

Aquat Toxicol. 2009 Feb 19;91(3):229-37. doi: 10.1016/j.aquatox.2008.11.007. Epub 2008 Nov 24.

DOI:10.1016/j.aquatox.2008.11.007
PMID:19110324
Abstract

Arsenic usually accumulates in soil, water and airborne particles, from which it is taken up by various organisms. Exposure to arsenic through food and drinking water is a major public health problem affecting some countries. At present there are limited laboratory data on the effects of arsenic exposure on early embryonic development and the mechanisms behind its toxicity. In this study, we used zebrafish as a model system to investigate the effects of arsenite on early development. Zebrafish embryos were exposed to a range of sodium arsenite concentrations (0-10.0mM) between 4 and 120h post-fertilization (hpf). Survival and early development of the embryos were not obviously influenced by arsenite concentrations below 0.5mM. However, embryos exposed to higher concentrations (0.5-10.0mM) displayed reduced survival and abnormal development including delayed hatching, retarded growth and changed morphology. Alterations in neural development included weak tactile responses to light (2.0-5.0mM, 30hpf), malformation of the spinal cord and disordered motor axon projections (2.0mM, 48hpf). Abnormal cardiac function was observed as bradycardia (0.5-2.0mM, 60hpf) and altered ventricular shape (2.0mM, 48hpf). Furthermore, altered cell proliferation (2.0mM, 24hpf) and apoptosis status (2.0mM, 24 and 48hpf), as well as abnormal genomic DNA methylation patterning (2.0mM, 24 and 48hpf) were detected in the arsenite-treated embryos. All of these indicate a possible relationship between arsenic exposure and developmental failure in early embryogenesis. Our studies suggest that the negative effects of arsenic on vertebrate embryogenesis are substantial.

摘要

砷通常积聚在土壤、水和空气中的颗粒物中,各种生物会从这些物质中摄取砷。通过食物和饮用水接触砷是影响一些国家的重大公共卫生问题。目前,关于砷暴露对早期胚胎发育的影响及其毒性背后的机制,实验室数据有限。在本研究中,我们使用斑马鱼作为模型系统来研究亚砷酸盐对早期发育的影响。在受精后4至120小时(hpf)之间,将斑马鱼胚胎暴露于一系列亚砷酸钠浓度(0 - 10.0mM)下。低于0.5mM的亚砷酸盐浓度对胚胎的存活和早期发育没有明显影响。然而,暴露于较高浓度(0.5 - 10.0mM)的胚胎显示存活率降低且发育异常,包括孵化延迟、生长迟缓以及形态改变。神经发育的改变包括对光的触觉反应减弱(2.0 - 5.0mM,30hpf)、脊髓畸形和运动轴突投射紊乱(2.0mM,48hpf)。观察到心脏功能异常表现为心动过缓(0.5 - 2.0mM,60hpf)和心室形状改变(2.0mM,48hpf)。此外,在经亚砷酸盐处理的胚胎中检测到细胞增殖改变(2.0mM,24hpf)和凋亡状态改变(2.0mM,24和48hpf),以及异常的基因组DNA甲基化模式(2.0mM,24和48hpf)。所有这些都表明砷暴露与早期胚胎发生中的发育失败之间可能存在关联。我们的研究表明,砷对脊椎动物胚胎发生具有重大负面影响。

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