Huang Lixing, Zuo Zhenghong, Zhang Youyu, Wang Chonggang
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, PR China.
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, PR China; Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, Xiamen University, Xiamen, PR China.
Aquat Toxicol. 2015 Jan;158:157-64. doi: 10.1016/j.aquatox.2014.10.024. Epub 2014 Nov 12.
There is a growing recognition that the toxic effects of chemical mixtures are been an important issue in toxicological sciences. Tributyltin (TBT) and benzo[a]pyrene (BaP) are widespread pollutants that occur simultaneously in the aquatic environments. This study was designed to examine comprehensively the combined effects of TBT and BaP on zebrafish (Danio rerio) embryos using toxicogenomic approach combined with biochemical detection and morphological analysis, and tried to gain insight into the mechanisms underlying the combined effects of TBT and BaP. The results of toxicogenomic data indicated that: (1) TBT cotreatment rescued the embryos from decreased hatching ratio caused by BaP alone, while the alteration of gene expression (in this article the phrase gene expression is used as a synonym to gene transcription, although in is acknowledged that gene expression can also be regulated by, e.g., translation and mRNA or protein stability) relative to zebrafish hatching in the BaP groups was resumed by the cotreatment with TBT; (2) BaP cotreatment decreased TBT-mediated dorsal curvature, and alleviated the perturbation of Notch pathway caused by TBT alone; (3) cotreatment with TBT decreased BaP-mediated bradycardia, which might be due to that TBT cotreatment alleviated the perturbation in expression of genes related to cardiac muscle cell development and calcium handling caused by BaP alone; 4) TBT cotreatment brought an antagonistic effect on the BaP-mediated oxidative stress and DNA damage. These results suggested that toxicogenomic approach was available for analyzing combined toxicity with high sensitivity and accuracy, which might improve our understanding and predictability for the combined effects of chemicals.
人们越来越认识到，化学混合物的毒性作用一直是毒理学领域的一个重要问题。三丁基锡（TBT）和苯并[a]芘（BaP）是广泛存在的污染物，同时出现在水生环境中。本研究旨在采用毒理基因组学方法，结合生化检测和形态学分析，全面研究TBT和BaP对斑马鱼（Danio rerio）胚胎的联合作用，并试图深入了解TBT和BaP联合作用的潜在机制。毒理基因组学数据结果表明：（1）TBT共同处理使胚胎从单独BaP导致的孵化率降低中恢复过来，而与BaP组中斑马鱼孵化相关的基因表达变化（在本文中，短语“基因表达”用作基因转录的同义词，尽管人们认识到基因表达也可通过例如翻译以及mRNA或蛋白质稳定性来调节）通过与TBT共同处理得以恢复；（2）BaP共同处理降低了TBT介导的背曲，并减轻了单独TBT引起的Notch信号通路的扰动；（3）与TBT共同处理降低了BaP介导的心动过缓，这可能是因为TBT共同处理减轻了单独BaP引起的与心肌细胞发育和钙处理相关基因表达的扰动；（4）TBT共同处理对BaP介导的氧化应激和DNA损伤产生拮抗作用。这些结果表明，毒理基因组学方法可用于高灵敏度和准确性地分析联合毒性，这可能会提高我们对化学物质联合作用的理解和预测能力。
