URBC, Namur Nanosafety Center (NNC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (FUNDP), 61 rue de Bruxelles, B-5000 Namur, Belgium.
Nanoscale. 2012 Nov 21;4(22):7168-84. doi: 10.1039/c2nr31785k.
The potential toxic effects of two types of copper(II) oxide (CuO) nanoparticles (NPs) with different specific surface areas, different shapes (rod or spheric), different sizes as raw materials and similar hydrodynamic diameter in suspension were studied on human hepatocarcinoma HepG2 cells. Both CuO NPs were shown to be able to enter into HepG2 cells and induce cellular toxicity by generating reactive oxygen species. CuO NPs increased the abundance of several transcripts coding for pro-inflammatory interleukins and chemokines. Transcriptomic data, siRNA knockdown and DNA binding activities suggested that Nrf2, NF-κB and AP-1 were implicated in the response of HepG2 cells to CuO NPs. CuO NP incubation also induced activation of MAPK pathways, ERKs and JNK/SAPK, playing a major role in the activation of AP-1. In addition, cytotoxicity, inflammatory and antioxidative responses and activation of intracellular transduction pathways induced by rod-shaped CuO NPs were more important than spherical CuO NPs. Measurement of Cu(2+) released in cell culture medium suggested that Cu(2+) cations released from CuO NPs were involved only to a small extent in the toxicity induced by these NPs on HepG2 cells.
研究了两种具有不同比表面积、不同形状（棒状或球状）、不同粒径（作为原料）但在悬浮液中具有相似水动力直径的氧化铜（CuO）纳米粒子（NPs）对人肝癌 HepG2 细胞的潜在毒性作用。结果表明，两种 CuO NPs 都能够进入 HepG2 细胞，并通过产生活性氧诱导细胞毒性。CuO NPs 增加了编码促炎细胞因子和趋化因子的几种转录本的丰度。转录组数据、siRNA 敲低和 DNA 结合活性表明，Nrf2、NF-κB 和 AP-1 参与了 HepG2 细胞对 CuO NPs 的反应。CuO NP 孵育还诱导了 MAPK 途径的激活，ERK 和 JNK/SAPK，在 AP-1 的激活中起主要作用。此外，棒状 CuO NPs 诱导的细胞毒性、炎症和抗氧化反应以及细胞内转导途径的激活比球形 CuO NPs 更为重要。细胞培养液中释放的 Cu（2+）的测量表明，从 CuO NPs 释放的 Cu（2+）阳离子仅在很小程度上参与了这些 NPs 对 HepG2 细胞的毒性。
