Low molecular weight silicones induce cell death in cultured cells

Carla Onnekink,Rita M Kappel,Ger J M Pruijn,Wilbert C Boelens

doi:10.1038/s41598-020-66666-7

Abstract

Women with silicone gel-filled breast implants are exposed to organosilicon compounds, in particular methylsiloxanes, as a result of ‘gel bleed’ and implant rupture. Although these silicones were originally considered to be inert, increasing evidence indicates that they can cause serious health problems. Here, we have analyzed the effects of microdroplets of the methylcyclosiloxanes, in particular D4, on the viability of cultured human cells. The exposure of Jurkat suspension and HeLa monolayer cells to D4 resulted in morphological changes of the cells. The analysis of molecular markers for apoptotic and necrotic processes not only demonstrated that caspases were activated and DNA was fragmented in Jurkat cells exposed to D4, but that also the permeability of the plasma membrane was altered. The induction of apoptotic pathways by D4 was substantiated by the inhibition of caspase activation in cells overexpressing Bcl-2. Cleavage of the caspase-3 substrate U1-70K appeared to be dependent on the D4 content and the efficiency of cleavage decreased with increasing size of the methylcyclosiloxanes (D4, D5 and D6). In addition to Jurkat cells, D4-induced U1-70K cleavage was also observed in HeLa cells, but not in HEp-2 cells. Taken together, these results indicate that D4 and, to a lesser extent, D5 can activate cell-death-related pathways in a cell type-specific fashion and suggest that this phenomenon may contribute to the development of Breast Implant Illness.

Highlights

In adipocytes[13,14]
As a reference for treatments affecting cell viability, the cells were treated in parallel with (i) anisomycin to induce apoptosis, or (ii) H2O2 to induce necrosis
The exposure of Jurkat cells to D4 in this timeframe did not lead to the characteristic morphological changes of apoptosis or necrosis, such as cell blebbing and cell swelling, which can be observed already 2 hours after the addition of anisomycin and H2O2, respectively (Fig. 1)

Summary

Introduction

It is important to note that silicone breast implants undergo changes in gel properties over time[15]. This may at least in part be caused by bacteria – normal breast tissue is known to be not sterile – that convert polydimethylsiloxanes into various silicon-containing molecules[16,17]. The resulting silicon-containing products can, at least in part, be less hydrophobic and this may increase the rate by which they are distributed through the body. Anything is known about the effect of silicone accumulations on the viability of cells. We have exposed cultured human cells to microdroplets of low molecular weight silicones and investigated the effects on cell viability and the appearance of cell death markers

Methods

Results

Conclusion