Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
A.R. Al-Jeraisy Chair for DNA Research, Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh, Saudi Arabia.
Adv Exp Med Biol. 2018;1048:163-174. doi: 10.1007/978-3-319-72041-8_10.
Nickel oxide nanoparticles (NiO-NPs) are increasingly used and concerns have been raised on its toxicity. Although a few studies have reported the toxicity of NiO-NPs, a comprehensive understanding of NiO-NPs toxicity in human cells is still lagging. In this study, we integrated transcriptomic approach and genotoxic evidence to depict the mechanism of NiO-NPs toxicity in human hepatocellular carcinoma (HepG2) cells. DNA damage analysis was done using comet assay, which showed 26-fold greater tail moment in HepG2 cells at the highest concentration of 100 μg/ml. Flow cytometric analysis showed concentration dependent enhancement in intracellular reactive oxygen species (ROS). Real-time PCR analysis of apoptotic (p53, bax, bcl2) and oxidative stress (SOD1) genes showed transcriptional upregulation. Transcriptome analysis using qPCR array showed over expression of mRNA transcripts related to six different cellular pathways. Our data unequivocally suggests that NiO-NPs induces oxidative stress, DNA damage, apoptosis and transcriptome alterations in HepG2 cells.
氧化镍纳米颗粒（NiO-NPs）的应用日益广泛，但其毒性也引起了人们的关注。尽管有一些研究报道了 NiO-NPs 的毒性，但人们对其在人类细胞中的毒性仍缺乏全面的了解。在这项研究中，我们综合了转录组学方法和遗传毒性证据，描绘了 NiO-NPs 对人肝癌（HepG2）细胞毒性的作用机制。彗星试验用于 DNA 损伤分析，结果显示在最高浓度为 100μg/ml 时，HepG2 细胞的尾部矩增加了 26 倍。流式细胞术分析显示，细胞内活性氧（ROS）的浓度依赖性增强。实时 PCR 分析凋亡（p53、bax、bcl2）和氧化应激（SOD1）基因显示转录上调。qPCR 阵列的转录组分析显示，与六个不同细胞通路相关的 mRNA 转录本表达过度。我们的数据明确表明，NiO-NPs 诱导 HepG2 细胞发生氧化应激、DNA 损伤、凋亡和转录组改变。
