Chen Hanyan, Wang Pingping, Du Zhongkun, Wang Guowei, Gao Shixiang
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, China.
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, China.
Aquat Toxicol. 2018 Jan;194:37-45. doi: 10.1016/j.aquatox.2017.11.001. Epub 2017 Nov 10.
Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) is an additive flame retardant of high production volume, and frequently detected in biota and environment. However, knowledge on its potential risk and toxicological mechanism still remains limited. In this study, DNA damage, transcriptomic responses and biochemical changes in the liver of zebrafish (Danio rerio) induced by TDCPP were investigated. Zebrafish was exposed to 45.81μg/L (1/100 (96h-LC)) and 229.05μg/L (1/20 (96h-LC)) TDCPP for 7 d. The reactive oxygen species (ROS) and GSH contents, in addition to antioxidant enzyme activities in the liver changed significantly, and the mRNA levels of genes related to oxidative stress were alerted in a dose-dependent and/or sex-dependent manner after exposure to TDCPP. Significant DNA damage in zebrafish liver was found, and olive tail moment increased in a concentration-dependent manner. Moreover, exposure of TDCPP at 45.81μg/L level activated the cell cycle arrest, DNA repair system and apoptosis pathway in male zebrafish, and 229.05μg/L TDCPP exposure inhibited those pathways in both male and female zebrafish. The cell apoptosis was confirmed in TUNEL assay as higher incidence of TUNEL-positive cells were observed in zebrafish exposed to 229.05μg/L TDCPP. Our results also indicated that males were more sensitive to TDCPP exposure compared with females. Taken together, our results showed that TDCPP could induce oxidative stress, cell cycle arrest, DNA damage and apoptosis in adult zebrafish liver in sex- and concentration-dependent manners.
磷酸三（1,3 - 二氯 - 2 - 丙基）酯（TDCPP）是一种大量生产的添加型阻燃剂，在生物群和环境中经常被检测到。然而，关于其潜在风险和毒理学机制的了解仍然有限。在本研究中，我们调查了TDCPP诱导斑马鱼（Danio rerio）肝脏中的DNA损伤、转录组反应和生化变化。斑马鱼暴露于45.81μg/L（1/100（96小时半数致死浓度））和229.05μg/L（1/20（96小时半数致死浓度））的TDCPP中7天。肝脏中的活性氧（ROS）和谷胱甘肽（GSH）含量以及抗氧化酶活性发生了显著变化，并且在暴露于TDCPP后，与氧化应激相关基因的mRNA水平以剂量依赖性和/或性别依赖性方式受到影响。在斑马鱼肝脏中发现了明显的DNA损伤，橄榄尾矩以浓度依赖性方式增加。此外，暴露于45.81μg/L水平的TDCPP激活了雄性斑马鱼的细胞周期停滞、DNA修复系统和凋亡途径，而暴露于229.05μg/L的TDCPP则抑制了雄性和雌性斑马鱼的这些途径。TUNEL检测证实了细胞凋亡，因为在暴露于229.05μg/L TDCPP的斑马鱼中观察到TUNEL阳性细胞的发生率更高。我们的结果还表明，与雌性相比，雄性对TDCPP暴露更敏感。综上所述，我们的结果表明，TDCPP可以以性别和浓度依赖性方式诱导成年斑马鱼肝脏中的氧化应激、细胞周期停滞、DNA损伤和凋亡。
