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

The multinucleation effect of silica
nanoparticles (SiNPs) had
been determined in our previous studies, but the relative mechanisms
of multinucleation and how the multinucleated cells are generated
were still not clear. This extensional study was conducted to investigate
the mechanisms underlying the formation of multinucleated 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,
karyokinesis 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 multinucleation. In summary, we confirmed the
hypothesis that aberrant cytokinesis and cell fusion resulted in multinucleation
in HepG2 cells after SiNPs exposure. Since cell fusion and multinucleation
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.