磷酸三（2-氯乙基）酯（TCEP）通过激活HepG2细胞中的人类癌症通路基因引发肝毒性。

Tris(2-chloroethyl) Phosphate (TCEP) Elicits Hepatotoxicity by Activating Human Cancer Pathway Genes in HepG2 Cells.

作者信息

M Al-Salem Abdullah, Saquib Quaiser, Siddiqui Maqsood A, Ahmad Javed, Al-Khedhairy Abdulaziz A

机构信息

Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

DNA Research Chair, Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

出版信息

Toxics. 2020 Nov 20;8(4):109. doi: 10.3390/toxics8040109.

Tris(2-chloroethyl) phosphate (TCEP) is one of the organophosphorus flame retardants (OPFRs) used in consumer commodities and have been detected in human body fluids. Research on TCEP-induced transcriptomic alterations and toxicological consequences in liver cells is still lacking. Herein, human hepatocellular (HepG2) cells were treated with 100, 200, and 400 μM TCEP for 3 days to quantify hepatotoxicity by MTT, NRU, and comet assays. Apoptosis, mitochondrial membrane potential (), oxidative stress, and Ca influx were measured by flow cytometry. A qPCR array was employed for transcriptomic analysis. MTT and NRU data showed 70.92% and 75.57% reduction in cell survival at 400 μM. In addition, 20-fold greater DNA damage was recorded at 400 μM. Cell cycle data showed 65.96% subG1 apoptotic peak in 400 μM treated cells. An elevated level of oxidative stress, esterase, Ca influx, and dysfunction were recorded in TCEP-treated cells. Out of 84 genes, the qPCR array showed upregulation of 17 genes and downregulation of 10 key genes belonging to human cancer pathways. Our study endorses the fact that TCEP possesses hepatotoxic potential at higher concentrations and prolonged exposure. Hence, TCEP may act as a cancer-inducing entity by provoking the gene network of human cancer pathways.

磷酸三（2-氯乙基）酯（TCEP）是一种用于消费品中的有机磷阻燃剂（OPFRs），已在人体体液中被检测到。目前仍缺乏关于TCEP诱导肝细胞转录组改变和毒理学后果的研究。在此，将人肝细胞（HepG2）细胞用100、200和400μM的TCEP处理3天，通过MTT、NRU和彗星试验来量化肝毒性。通过流式细胞术测量细胞凋亡、线粒体膜电位、氧化应激和钙内流。采用qPCR阵列进行转录组分析。MTT和NRU数据显示，在400μM时细胞存活率分别降低了70.92%和75.57%。此外，在400μM时记录到的DNA损伤增加了20倍。细胞周期数据显示，在400μM处理的细胞中，亚G1期凋亡峰为65.96%。在TCEP处理的细胞中记录到氧化应激、酯酶、钙内流水平升高以及线粒体功能障碍。在84个基因中，qPCR阵列显示17个基因上调，10个属于人类癌症通路的关键基因下调。我们的研究证实了这样一个事实，即TCEP在高浓度和长时间暴露时具有肝毒性潜力。因此，TCEP可能通过激发人类癌症通路的基因网络而成为一种致癌实体。