Mechanisms of hexabromocyclododecanes induced developmental toxicity in marine medaka (Oryzias melastigma) embryos
Mechanisms of hexabromocyclododecanes induced developmental toxicity in marine medaka (Oryzias melastigma) embryos
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DOI：
10.1016/j.aquatox.2014.04.010
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发表时间：
2014-07-01
影响因子：
4.5
通讯作者：
Shi, Dalin
中科院分区：
文献类型：
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作者：
Hong, Haizheng;Li, Dongmei;Shi, Dalin
六溴环十二烷（HBCD）作为添加剂溴化阻燃剂被广泛使用，现已成为环境介质和生物群中普遍存在的污染物，包括海洋环境和海洋生物。然而，六溴环十二烷对海洋鱼类的影响并不为人所知。在这项研究中，海洋青鳉（Oryzias melanoma）的胚胎被用于评估六溴环十二烷的发育毒性。将新鲜受精的青鳉胚胎暴露于不同浓度的工业六溴环十二烷（tHBCD，0、5、20和50微克/升），直至第一个鱼苗阶段，并检查孵化成功率、形态和心脏功能。在所有接触组（5、20和50微克/升）中，tHBCD显著增加了胚胎心跳。静脉窦-动脉球（SV-BA）距离的测量结果表明，在20和50微克/升的接触浓度下，tHBCD显著扩大了SV-BA距离。tHBCD还以剂量依赖性方式诱导第一个鱼苗阶段的畸形率，其中心包水肿和卵黄囊水肿的形成是最常见的畸形。此外，本研究中胚胎中的六溴环十二烷总异构体（六溴环十二烷西格玛）浓度与环境水平相当，并随着接触时间的增加而增加。此外，暴露于tHBCD还诱导了8-oxodG的水平，这是一种典型的氧化性DNA损伤。通过TUNEL试验、基于凝胶的定量蛋白质组学方法和测量几种应激反应基因（如p53、TNE-α、IL-1 β、CYP 1A、考克斯-1和考克斯-2）的表达以及半胱天冬酶的活性，进一步探索了六溴环十二烷诱导的发育毒性机制。结果表明，六溴环十二烷在环境实际浓度下的暴露可诱导氧化应激和细胞凋亡，并抑制核苷酸和蛋白质合成，这些共同导致发育毒性，特别是在心血管系统中，在O.黑星(C)2014爱思唯尔有限公司版权所有。
Hexabromocyclododecanes (HBCDs) are widely used as additive brominated flame retardants, and are now ubiquitous contaminants in the environmental media and biota, including the marine environment and marine organisms. However, the impacts of HBCDs on marine fish are not well known. In this study the embryos of marine medaka (Oryzias melastigma) were used to assess the developmental toxicity of HBCDs. Freshly fertilized marine medaka embryos were exposed to various concentrations of technical HBCD (tHBCD, 0, 5, 20 and 50 mu g/L) until the first fry stage, and hatch success, morphology and cardiac function were examined. In all the exposure groups (5,20 and 50 mu g/L) tHBCD significantly increased the embryo heart beats. The measurement of sinus venosus-bulbus arteriosus (SV-BA) distance indicated that tHBCD significantly enlarged the SV-BA distance at exposure concentrations of 20 and 50 mu g/L. The malformation rate at the first fry stage was also induced by tHBCD in a dose dependent manner, with the formation of pericardial edema and yolk sac edema as the most frequently observed malformation. In addition, the concentrations of total HBCD isomers (Sigma HBCDs) in embryos in the current study were comparative with environmental levels and increased with increasing exposure duration. Furthermore, exposure to tHBCD also induced the level of 8-oxodG, a representative oxidative DNA damage. The mechanisms of HBCD-induced developmental toxicity were further explored by TUNEL assay, gel-based quantitative proteomic approach and measurement of the expression of several stress responsive genes, such as p53, TNE-alpha, IL-1 beta, CYP1A, COX-1 and COX-2, together with the activities of caspases. The results suggested that HBCDs exposure at environmentally realistic concentrations induced oxidative stress and apoptosis, and suppressed nucleotide and protein synthesis, which all together resulted in developmental toxicity, particularly in the cardiovascular system, in the embryos of O. melastigrna. (C) 2014 Elsevier B.V. All rights reserved.