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Oxidative stress, cell cycle arrest, DNA damage and apoptosis in adult zebrafish (Danio rerio) induced by tris(1,3-dichloro-2-propyl) phosphate
Aquatic Toxicology ( IF 4.1 ) Pub Date : 2017-11-10 , DOI: 10.1016/j.aquatox.2017.11.001
Hanyan Chen , Pingping Wang , Zhongkun Du , Guowei Wang , Shixiang Gao

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 45.81 μg/L (1/100 (96h-LC50)) and 229.05 μg/L (1/20 (96h-LC50)) 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 45.81 μg/L level activated the cell cycle arrest, DNA repair system and apoptosis pathway in male zebrafish, and 229.05 μg/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 229.05 μg/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.



中文翻译:

三(1,3-二氯-2-丙基)磷酸酯诱导的成年斑马鱼(Danio rerio)的氧化应激,细胞周期停滞,DNA损伤和细胞凋亡

磷酸三(1,3-二氯-2-丙基)酯(TDCPP)是一种高产量的添加剂型阻燃剂,经常在生物区系和环境中被检测到。但是,关于其潜在危险和毒理学机理的知识仍然很有限。在这项研究中,研究了DNA损伤,转录组反应和TDCPP诱导的斑马鱼肝脏(Danio rerio)的生化变化。斑马鱼暴露于45.81μg/ L(1/100(96h-LC 50))和229.05μg/ L(1/20(96h-LC 50)))TDCPP进行7 d。暴露于肝脏后,除肝脏中的抗氧化酶活性外,活性氧(ROS)和GSH含量也发生了显着变化,并且与氧化应激相关的基因的mRNA水平以剂量依赖性和/或性别依赖性方式被警告。 TDCPP。在斑马鱼肝脏中发现了明显的DNA损伤,并且橄榄尾矩以浓度依赖性方式增加。此外,TDCPP暴露于45.81μg/ L水平可激活雄性斑马鱼的细胞周期阻滞,DNA修复系统和凋亡途径,而229.05μg/ L TDCPP暴露可抑制雄性和雌性斑马鱼的这些途径。在暴露于229.05μg/ L TDCPP的斑马鱼中观察到更高的TUNEL阳性细胞发生率,因此在TUNEL分析中证实了细胞凋亡。我们的结果还表明,与女性相比,男性对TDCPP暴露更敏感。两者合计,我们的结果表明,TDCPP可以以性别和浓度依赖性的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。

更新日期:2017-11-10
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