Aberrant Cytokinesis and Cell Fusion Result in Multinucleation in HepG2 Cells Exposed to Silica Nanoparticles

作者：Yu, Yongbo; Duan, Junchao; Geng, Weijia; Li, Qiuling; Jiang, Lizhen; Li, Yang; Yu, Yang; Sun, Zhiwei^*

来源：Chemical Research in Toxicology, 2015, 28(3): 490-500.

DOI：10.1021/tx500473h

• CHROMOSOMAL PASSENGER COMPLEX
• DNA-DAMAGE
• DEPENDENT KINASES
• TUMOR-CELLS
• IN-VIVO
• DIVISION
• APOPTOSIS
• CYTOTOXICITY
• CHECKPOINT
• TOXICITY

The multinucleation effect of silica nanoparticles (SiNPs) had been determined in our previous studies, but the relative mechanisms of multinudeation and how the multinudeated cells are generated were still not cleat. This extensional study was Conducted to investigate the mechanisms underlying the formation of multinudeated cells after SiNPs exposure. We first investigated cellular multinucleation, then performed time-lapse confocal imaging to certify whether the multinucleated cells resulted from cell fusion or abnormal cell division: Our results confirmed for the first time that there are three patterns contributing to the SiNPs-induced multinucleation in HepG2 cells: cell fusion, karyoldnesis without cytokinesis, and cytokinesis followed by fusion. The chromosomal passenger complex (CPC) deficiency and cell cycle arrest in G1/S and G2/M checkpoints may be responsible for the cell aberrant cytokinesis. The activated MAPK/ERK1/2 signaling and decreased mitosis related proteins might be the underlying mechanism of cell cycle arrest and thus multinudeation. In summary, we confirmed the hypothesis that aberrant cytokinesis and cell fusion resulted in multinudeation in RepG2 cells after SiNPS exposure. Since cell fusion and multinudeation were involved in genetic instability and tumor development, this study suggests the potential ability of SiNPs to induce cellular genetic instability. These findings raise concerns with regard to human health hazards and environmental risks with SiNPs exposure.

• 出版日期2015-3
• 单位首都医科大学