Aberrant Cytokinesis and CellFusion Result in Multinucleationin HepG2 Cells Exposed to Silica Nanoparticles.

The multinucleation effect of silicananoparticles (SiNPs) hadbeen determined in our previous studies, but the relative mechanismsof multinucleation and how the multinucleated cells are generatedwere still not clear. This extensional study was conducted to investigatethe mechanisms underlying the formation of multinucleated cells afterSiNPs exposure. We first investigated cellular multinucleation, thenperformed time-lapse confocal imaging to certify whether the multinucleatedcells resulted from cell fusion or abnormal cell division. Our resultsconfirmed for the first time that there are three patterns contributingto 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 cyclearrest in G1/S and G2/M checkpoints may be responsible for the cellaberrant cytokinesis. The activated MAPK/ERK1/2 signaling and decreasedmitosis related proteins might be the underlying mechanism of cellcycle arrest and thus multinucleation. In summary, we confirmed thehypothesis that aberrant cytokinesis and cell fusion resulted in multinucleationin HepG2 cells after SiNPs exposure. Since cell fusion and multinucleationwere involved in genetic instability and tumor development, this studysuggests the potential ability of SiNPs to induce cellular geneticinstability. These findings raise concerns with regard to human healthhazards and environmental risks with SiNPs exposure. [ABSTRACT FROM AUTHOR]