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Transcriptome profiling of HepG2 cells exposed to the flame retardant 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO)†
Toxicology Research ( IF 2.2 ) Pub Date : 2018-03-12 00:00:00 , DOI: 10.1039/c8tx00006a Boris V. Krivoshiev 1, 2, 3, 4, 5 , Gerrit T. S. Beemster 1, 3, 4, 5, 6 , Katrien Sprangers 1, 3, 4, 5, 6 , Bart Cuypers 3, 4, 5, 7, 8 , Kris Laukens 3, 4, 5, 7, 8 , Ronny Blust 1, 2, 3, 4, 5 , Steven J. Husson 1, 2, 3, 4, 5
Toxicology Research ( IF 2.2 ) Pub Date : 2018-03-12 00:00:00 , DOI: 10.1039/c8tx00006a Boris V. Krivoshiev 1, 2, 3, 4, 5 , Gerrit T. S. Beemster 1, 3, 4, 5, 6 , Katrien Sprangers 1, 3, 4, 5, 6 , Bart Cuypers 3, 4, 5, 7, 8 , Kris Laukens 3, 4, 5, 7, 8 , Ronny Blust 1, 2, 3, 4, 5 , Steven J. Husson 1, 2, 3, 4, 5
Affiliation
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The flame retardant, 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO), has been receiving great interest given its superior fire protection properties, and its predicted low level of persistence, bioaccumulation, and toxicity. However, empirical toxicological data that are essential for a complete hazard assessment are severely lacking. In this study, we attempted to identify the potential toxicological modes of action by transcriptome (RNA-seq) profiling of the human liver hepatocellular carcinoma cell line, HepG2. Such insight may help in identifying compounds of concern and potential toxicological phenotypes. DOPO was found to have little cytotoxic potential, with lower effective concentrations compared to other flame retardants studied in the same cell line. Differentially expressed genes revealed a wide range of molecular effects including changes in protein, energy, DNA, and lipid metabolism, along with changes in cellular stress response pathways. In response to 250 μM DOPO, the most perturbed biological processes were fatty acid metabolism, androgen metabolism, glucose transport, and renal function and development, which is in agreement with other studies that observed similar effects of other flame retardants in other species. However, treatment with 2.5 μM DOPO resulted in very few differentially expressed genes and failed to indicate any potential effects on biology, despite such concentrations likely being orders of magnitude greater than would be encountered in the environment. This, together with the low levels of cytotoxicity, supports the potential replacement of the current flame retardants by DOPO, although further studies are needed to establish the nephrotoxicity and endocrine disruption of DOPO.
中文翻译：
暴露于阻燃剂9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-氧化物（DOPO）的HepG2细胞的转录组分析†
阻燃剂9,10-二氢-9-氧杂-10磷菲10氧化物（DOPO）由于其优越的防火性能以及预计的低持久性，生物蓄积性和毒性而备受关注。但是，严重缺乏完整的危害评估所必需的经验毒理学数据。在这项研究中，我们试图通过人类肝肝癌细胞株HepG2的转录组（RNA-seq）分析来确定潜在的毒理作用模式。这样的洞察力可能有助于确定所关注的化合物和潜在的毒理学表型。与在同一细胞系中研究的其他阻燃剂相比，发现DOPO具有极小的细胞毒性潜力，且有效浓度较低。差异表达的基因揭示了广泛的分子效应，包括蛋白质，能量，DNA和脂质代谢的变化，以及细胞应激反应途径的变化。响应250μMDOPO，最受干扰的生物学过程是脂肪酸代谢，雄激素代谢，葡萄糖转运以及肾功能和发育，这与其他研究观察到的其他物种中其他阻燃剂的类似作用相吻合。然而，用2.5μMDOPO处理导致差异表达的基因极少，并且未能表明对生物学的任何潜在影响，尽管这种浓度可能比在环境中遇到的浓度高几个数量级。再加上低水平的细胞毒性，
更新日期：2018-03-12
中文翻译：
暴露于阻燃剂9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-氧化物（DOPO）的HepG2细胞的转录组分析†
阻燃剂9,10-二氢-9-氧杂-10磷菲10氧化物（DOPO）由于其优越的防火性能以及预计的低持久性，生物蓄积性和毒性而备受关注。但是，严重缺乏完整的危害评估所必需的经验毒理学数据。在这项研究中，我们试图通过人类肝肝癌细胞株HepG2的转录组（RNA-seq）分析来确定潜在的毒理作用模式。这样的洞察力可能有助于确定所关注的化合物和潜在的毒理学表型。与在同一细胞系中研究的其他阻燃剂相比，发现DOPO具有极小的细胞毒性潜力，且有效浓度较低。差异表达的基因揭示了广泛的分子效应，包括蛋白质，能量，DNA和脂质代谢的变化，以及细胞应激反应途径的变化。响应250μMDOPO，最受干扰的生物学过程是脂肪酸代谢，雄激素代谢，葡萄糖转运以及肾功能和发育，这与其他研究观察到的其他物种中其他阻燃剂的类似作用相吻合。然而，用2.5μMDOPO处理导致差异表达的基因极少，并且未能表明对生物学的任何潜在影响，尽管这种浓度可能比在环境中遇到的浓度高几个数量级。再加上低水平的细胞毒性，
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