Abstract

Aluminum oxide nanoparticles (Al₂O₃-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 Al₂O₃-NPs on the environment and on human health has not been well studied. In this investigation, we evaluated the cytotoxic effects of Al₂O₃-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 Al₂O₃-NPs reduced hMSC viability in a dose- and time-dependent manner. Nuclear condensation and fragmentation, chromosomal DNA fragmentation, and cytoplasmic vacuolization were observed in Al₂O₃-NP-exposed cells. The nuclear morphological changes indicated that Al₂O₃-NPs alter cell cycle progression and gene expression. The cell cycle distribution revealed that Al₂O₃-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, Al₂O₃-NPs induced the upregulation of cell cycle response genes, including EGR1, E2F1, and CCND1. Our results suggested that exposure to Al₂O₃-NPs could cause acute cytotoxic effects in hMSCs through cell cycle regulatory genes.