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Effects of cerium oxide nanoparticles on differentiated/undifferentiated human intestinal Caco-2 cells
Chemico-Biological Interactions ( IF 5.1 ) Pub Date : 2018-01-31 , DOI: 10.1016/j.cbi.2018.01.018
Laura Vila , Alba García-Rodríguez , Constanza Cortés , Antonia Velázquez , Noel Xamena , Adriana Sampayo-Reyes , Ricard Marcos , Alba Hernández

Since ingestion constitute one of the main routes of nanoparticles (NPs) exposure, intestinal cells seems to be a suitable choice to evaluate their potential harmful effects. Caco-2 cells, derived from a human colon adenocarcinoma, have the ability to differentiate forming consistent cell monolayer structures. For these reasons Caco-2 cells, both in their undifferentiated or differentiated state, are extendedly used. We have used well-structured monolayers of differentiated Caco-2 cells, as a model of intestinal barrier, to evaluate potential harmful effects associated to CeO2NPs exposure via ingestion. Different parameters such as cell toxicity, monolayer integrity and permeability, cell internalization, translocation through the monolayer, and induction of DNA damage were evaluated. No toxic effects of CeO2NPs were observed, independently of the differentiated state of the Caco-2 cells. In the same way, no effects on the monolayer integrity/permeability were observed. Although important cell uptake was demonstrated in undifferentiated cells (by using confocal microscopy), CeO2NPs remained mostly attached to the apical membrane in the differentiated cells. In spite of this apparent lack of uptake in differentiated cells, translocation of CeO2NPs to the basolateral chamber was observed by using confocal microscopy. Finally no genotoxic effects were observed when the comet assay was used, although decreases in the levels of oxidized bases were observed, supporting the antioxidant role of CeO2NPs.



中文翻译:

氧化铈纳米粒子对人肠道Caco-2细胞分化/未分化的影响

由于摄入是纳米颗粒(NPs)暴露的主要途径之一,因此肠细胞似乎是评估其潜在有害作用的合适选择。来源于人结肠腺癌的Caco-2细胞具有分化形成一致的细胞单层结构的能力。由于这些原因,长期使用处于未分化或分化状态的Caco-2细胞。我们已经使用结构良好的分化Caco-2细胞单层膜作为肠道屏障模型,以评估与通过摄入CeO 2 NPs暴露相关的潜在有害影响。评估了不同的参数,例如细胞毒性,单层完整性和通透性,细胞内在化,通过单层的易位以及DNA损伤的诱导。CeO无毒作用观察到2个NP,与Caco-2细胞的分化状态无关。以相同的方式,未观察到对单层完整性/渗透性的影响。尽管在未分化的细胞中证实了重要的细胞摄取(通过共聚焦显微镜),但CeO 2 NPs大部分仍附着在分化细胞的顶膜上。尽管在分化的细胞中明显缺乏摄取,但是通过使用共聚焦显微镜观察到了CeO 2 NPs向基底外侧室的移位。最后,尽管使用了彗星试验,但未观察到遗传毒性作用,尽管观察到了氧化碱基水平的下降,这支持了CeO 2 NPs的抗氧化作用。

更新日期:2018-01-31
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