Zoology Department, College of Sciences, King Saud University, Riyadh, Saudi Arabia.
Chair for DNA Research, Zoology Department, College of Sciences, King Saud University, Riyadh, Saudi Arabia.
J Appl Toxicol. 2021 May;41(5):861-873. doi: 10.1002/jat.4158. Epub 2021 Feb 28.
Tris(1-chloro-2-propyl)phosphate (TCPP) is a chlorinated organophosphorus flame retardant (OPFR) widely used in consumer goods after the phaseout of brominated flame retardants (BFRs). TCPP can percolate into the indoor and outdoor dusts, leading to its detection in the human body fluids (urine, breast milk) and placenta. However, TCPP has not been studied so far for its toxicity in the human vascular system. Hence, we have used human umbilical vein endothelial cells (HUVECs) and exposed them to TCPP ranging from low to high (5-400 μM) concentrations for 24 h. Cytotoxicity analysis by MTT and NRU assays exhibited 15.27% and 20.56%, 21.67%, and 48.67% survival decline of cells only at 200 and 400 μM. Comet assay data showed DNA damage from 50 to 400 μM with Olive tail moment (OTM) values between 1.03 and 35.59, respectively. TCPP-exposed HUVECs exhibited 1.09 and 1.39-fold greater intracellular reactive oxygen species (ROS) at 25 and 400 μM, indicating oxidative stress. HUVEC mitochondrial membrane potential (ΔΨm) measurements showed 1.16 and 1.48-fold higher fluorescence of Rh123 dye at 25 and 400 μM, confirming mitochondrial dysfunction. Flow cytometric data demonstrated 5.1%-58.8% cells in SubG1 apoptotic phase at 5 and 400 μM TCPP. Our novel data revealed that TCPP is a genotoxic and apoptotic inducer, which may trigger alike responses in human vascular system. Overall, detailed in vivo studies are warranted on the transcriptional and translations effects of TCPP.
磷酸三(1-氯-2-丙基)酯(TCPP)是一种氯化有机磷阻燃剂(OPFR),在溴化阻燃剂(BFRs)淘汰后广泛用于消费品。TCPP 可以渗透到室内和室外灰尘中,导致其在人体液(尿液、母乳)和胎盘。然而,目前尚未研究 TCPP 在人体血管系统中的毒性。因此,我们使用人脐静脉内皮细胞(HUVECs),并将其暴露于低至高(5-400μM)浓度的 TCPP 中 24 小时。MTT 和 NRU 测定法的细胞毒性分析显示,仅在 200 和 400μM 时细胞存活率分别下降了 15.27%和 20.56%,21.67%和 48.67%。彗星试验数据显示,50-400μM 的 DNA 损伤,Olive 尾矩(OTM)值分别为 1.03-35.59。暴露于 TCPP 的 HUVECs 在 25 和 400μM 时表现出 1.09 和 1.39 倍更高的细胞内活性氧(ROS),表明氧化应激。HUVEC 线粒体膜电位(ΔΨm)测量显示,25 和 400μM 时 Rh123 染料的荧光分别增加了 1.16 和 1.48 倍,证实了线粒体功能障碍。流式细胞术数据表明,在 5 和 400μM TCPP 时,有 5.1%-58.8%的细胞处于 SubG1 凋亡期。我们的新数据表明,TCPP 是一种遗传毒性和凋亡诱导剂,可能会在人体血管系统中引发类似的反应。总体而言,需要对 TCPP 的转录和翻译效应进行详细的体内研究。