Department of Veterinary Sciences, University of Pisa, San Piero a Grado (PI) 56122, Italy; Department of Biology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Department of Biology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Toxicol Appl Pharmacol. 2019 May 15;371:84-94. doi: 10.1016/j.taap.2019.04.004. Epub 2019 Apr 8.
Organophosphate esters (OPEs) are frequently used as replacements for the banned polybrominated diphenyl ether (PBDEs). Since OPEs are structurally similar to organophosphate pesticides, exposure and toxicity of these compounds is of significant societal and scientific interest. Cytotoxicity (MTT), biotransformation (cyp1a1) and oxidative stress responses (gpx1, gr, gsta2, cat) were investigated in H4IIE cells exposed for 48 h to four different OPEs (tributyl phosphate (TBP), tris(2-butoxyethyl) phosphate (TBOEP), tris-(2-chloroethyl) phosphate (TCEP) and triphenyl phosphate (TPP)). MTT assay revealed a dose-dependent decrease of cell viability following exposure to TBP, TBOEP, TCEP and TPP. Cells treated with TBP and TBOEP exhibited significant increase of cyp1a1 at the highest tested concentration, at transcriptional and enzymatic (MROD) levels. Significant increases of oxidative stress markers were observed after exposure to TBP and TBOEP. On the other hand, cells treated with TCEP and TPP showed opposite trends between cyp1a1 mRNA and enzymatic activities. Furthermore, exposure to TCEP increased gst and cat especially at the highest concentration tested, whereas TPP produced significant changes only for gr and cat at the highest concentration. In conclusion, OPEs produced compound and concentration-specific effects on biotransformation and oxidative stress processes. Overall, our results suggest the participation of multiple mechanisms of detoxification in defense of OPEs exposure with different modes of action depending on their chemical structure.
有机磷酸酯（OPEs）经常被用作已禁用的多溴二苯醚（PBDEs）的替代品。由于 OPEs 在结构上与有机磷酸酯农药相似，因此这些化合物的暴露和毒性引起了社会和科学界的极大关注。本研究采用人肝癌细胞（H4IIE），研究了 48 小时暴露于四种不同 OPEs（磷酸三丁酯（TBP）、磷酸三（2-丁氧基乙基）酯（TBOEP）、磷酸三（2-氯乙基）酯（TCEP）和磷酸三苯酯（TPP））对细胞活力（MTT）、生物转化（cyp1a1）和氧化应激反应（gpx1、gr、gsta2、cat）的影响。MTT 试验结果表明，随着 TBP、TBOEP、TCEP 和 TPP 暴露剂量的增加，细胞活力逐渐降低。TBP 和 TBOEP 处理组细胞在最高测试浓度下，在转录和酶（MROD）水平上均表现出显著的 cyp1a1 增加。TBP 和 TBOEP 处理组细胞的氧化应激标志物明显增加。另一方面，TCEP 和 TPP 处理组细胞的 cyp1a1 mRNA 和酶活性之间呈相反趋势。此外，TCEP 暴露组的 gst 和 cat 尤其在最高测试浓度下显著增加，而 TPP 仅在最高浓度下对 gr 和 cat 产生显著变化。综上所述，OPEs 对生物转化和氧化应激过程产生了化合物和浓度特异性影响。总体而言，我们的结果表明，多种解毒机制参与了 OPEs 暴露的防御，其作用模式取决于它们的化学结构。
