State Key Lab of Pollutant Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, P.R. China.
Environ Sci Technol. 2012 Oct 2;46(19):10758-64. doi: 10.1021/es301804t. Epub 2012 Sep 12.
Dechlorane plus (DP), a chlorinated flame retardant, has been widely detected in different environmental matrices and biota. However, toxicity data for DP have seldom been reported. In the present study, we investigated hepatic oxidative stress, DNA damage, and transcriptomic and metabonomic responses of male mice administered 500 mg/kg, 2000 mg/kg, and 5000 mg/kg of DP by gavage for 10 days. The results showed that DP exposure increased the level of superoxide dismutase (SOD) and 8-hydroxy-2-deoxyguanosine (8-OHdG). The microarray-based transcriptomic results demonstrated that DP exposure led to significant alteration of gene expression involved in carbohydrate, lipid, nucleotide, and energy metabolism, as well as signal transduction processes. The NMR-based metabonomic analyses corroborated these results showing changes of metabolites associated with the above altered mechanisms. Our results demonstrate that an oral exposure to DP can induce hepatic oxidative damage and perturbations of metabolism and signal transduction. These observations provide novel insight into toxicological effects and mechanisms of action of DP at the transcriptomic and metabonomic levels.
六氯丁二烯（DP）是一种氯化阻燃剂，已在不同的环境基质和生物群中广泛检出。然而，关于 DP 的毒性数据却很少有报道。在本研究中，我们通过灌胃方式给予雄性小鼠 500mg/kg、2000mg/kg 和 5000mg/kg 的 DP，连续 10 天，研究了 DP 对其肝脏氧化应激、DNA 损伤以及转录组和代谢组的影响。结果表明，DP 暴露会增加超氧化物歧化酶（SOD）和 8-羟基-2-脱氧鸟苷（8-OHdG）的水平。基于微阵列的转录组学结果表明，DP 暴露会导致参与碳水化合物、脂质、核苷酸和能量代谢以及信号转导过程的基因表达发生显著改变。基于 NMR 的代谢组学分析证实了这些结果，表明与上述改变机制相关的代谢物发生了变化。我们的研究结果表明，口服 DP 暴露会导致肝脏氧化损伤以及代谢和信号转导的紊乱。这些观察结果为 DP 在转录组和代谢组水平上的毒理学效应和作用机制提供了新的见解。
