Periasamy Vaiyapuri Subbarayan, Athinarayanan Jegan, Alshatwi Ali A
Nanobiotechnology and Molecular Biology Research Laboratory, Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Biotechnol Appl Biochem. 2016 May;63(3):320-7. doi: 10.1002/bab.1368. Epub 2015 Jul 14.
Aluminum oxide nanoparticles (Al2 O3 -NPs) are important ceramic materials that have been used in a variety of commercial and industrial applications. However, the impact of acute and chronic exposure to Al2 O3 -NPs on the environment and on human health has not been well studied. In this investigation, we evaluated the cytotoxic effects of Al2 O3 -NPs on human mesenchymal stem cells (hMSCs) by using a cell viability assay and observing cellular morphological changes, analyzing cell cycle progression, and monitoring the expression of cell cycle response genes (PCNA, EGR1, E2F1, CCND1, CCNC, CCNG1, and CYCD3). The Al2 O3 -NPs reduced hMSC viability in a dose- and time-dependent manner. Nuclear condensation and fragmentation, chromosomal DNA fragmentation, and cytoplasmic vacuolization were observed in Al2 O3 -NP-exposed cells. The nuclear morphological changes indicated that Al2 O3 -NPs alter cell cycle progression and gene expression. The cell cycle distribution revealed that Al2 O3 -NPs cause cell cycle arrest in the sub-G0-G1 phase, and this is associated with a reduction in the cell population in the G2/M and G0/G1 phases. Moreover, Al2 O3 -NPs induced the upregulation of cell cycle response genes, including EGR1, E2F1, and CCND1. Our results suggested that exposure to Al2 O3 -NPs could cause acute cytotoxic effects in hMSCs through cell cycle regulatory genes.
氧化铝纳米颗粒（Al2O3-NPs）是重要的陶瓷材料，已被用于各种商业和工业应用。然而，急性和慢性暴露于Al2O3-NPs对环境和人类健康的影响尚未得到充分研究。在本研究中，我们通过细胞活力测定、观察细胞形态变化、分析细胞周期进程以及监测细胞周期反应基因（PCNA、EGR1、E2F1、CCND1、CCNC、CCNG1和CYCD3）的表达，评估了Al2O3-NPs对人间充质干细胞（hMSCs）的细胞毒性作用。Al2O3-NPs以剂量和时间依赖性方式降低hMSC活力。在暴露于Al2O3-NPs的细胞中观察到核浓缩和碎片化、染色体DNA碎片化以及细胞质空泡化。核形态变化表明Al2O3-NPs改变细胞周期进程和基因表达。细胞周期分布显示，Al2O3-NPs导致细胞周期停滞在亚G0-G1期，这与G2/M期和G0/G1期细胞群体的减少有关。此外，Al2O3-NPs诱导细胞周期反应基因上调，包括EGR1、E2F1和CCND1。我们的结果表明，暴露于Al2O3-NPs可能通过细胞周期调控基因在hMSCs中引起急性细胞毒性作用。
