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邻苯二甲酸二乙基己酯对人淋巴母细胞的细胞死亡效应

Cell Death Effects of the Phthalate 2-Ethyl-1-Hexanol on Human Linfoblast Cells.

作者信息

Rios Karoline, Vélez Christian, Zayas Beatriz

机构信息

School of Science and Technology and Environment, Universidad Ana G. Méndez, San Juan, Puerto Rico.

出版信息

Open J Apoptosis. 2019 Jan;8:1-15. doi: 10.4236/ojapo.2019.81001. Epub 2019 Jan 31.

Abstract

Phthalates have been used in a wide variety of consumer goods. Their versatility as plasticizers has translated into worldwide use in a vast array of consumer products. These compounds can leach into matrices, such as food and liquids that can be routed for human exposure. One of the most used phthalates is Diethylhexyl phthalate (DEHP). Diethylhexyl phthalate and its metabolite 2-ethyl-1-hexanol (2-EH) have demonstrated biological effects which merit further evaluation. In this work, we expand on our previous work with DEHP and screen the 2-EH metabolite for different cell death endpoints such as growth inhibition, apoptosis, autophagy, caspase activation, DNA fragmentation, and cell cycle arrest using fluorophores and the NC3000 instrument. Significant results ( < 0.05) revealed higher toxicity for the 2-EH metabolite when compared to DEHP. Also, 2-EH presented apoptosis induction with characteristic hallmarks, such as loss of mitochondrial membrane potential, caspase activation, DNA fragmentation and cell cycle arrest at the S phase. In addition, the presence of autophagosome was detected through L3CB protein staining. We conclude that 2-EH presents differences in cell death endpoints that interestingly differ from the DEHP parent compound. Further studies are needed to establish the molecular pathways responsible for the observed effects.

摘要

邻苯二甲酸盐已被广泛应用于各种消费品中。它们作为增塑剂的多功能性已使其在全球范围内被大量用于各类消费品。这些化合物可渗入食物和液体等基质中,进而进入人体。最常用的邻苯二甲酸盐之一是邻苯二甲酸二(2-乙基己基)酯(DEHP)。邻苯二甲酸二(2-乙基己基)酯及其代谢物2-乙基-1-己醇(2-EH)已显示出值得进一步评估的生物学效应。在这项工作中,我们在之前对DEHP研究的基础上进行拓展,使用荧光团和NC3000仪器,针对不同的细胞死亡终点,如生长抑制、凋亡、自噬、半胱天冬酶激活、DNA片段化和细胞周期阻滞,对2-EH代谢物进行筛选。显著结果(<0.05)表明,与DEHP相比,2-EH代谢物具有更高的毒性。此外,2-EH呈现出凋亡诱导作用,并具有特征性标志,如线粒体膜电位丧失、半胱天冬酶激活、DNA片段化以及细胞周期在S期阻滞。另外,通过L3CB蛋白染色检测到了自噬体的存在。我们得出结论,2-EH在细胞死亡终点方面存在差异,有趣的是,这些差异与DEHP母体化合物不同。需要进一步研究以确定导致观察到的效应的分子途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0895/7678683/798e818d0cc3/nihms-1046424-f0001.jpg

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