Low molecular weight silicones induce cell death in cultured cells

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.

What Is the Cause of Toxicity of Silicone Oil?

“…In our study, the bright green fluorescence with different proportion was observed in the cells in both liquid and emulsified LMWC groups, indicating that the apoptotic process was involved in the ARPE-19 cell death pathway after LMWC treatment. This is consistent with the results of another in vitro study in which D4 induced the death of Jurkat cells with several apoptotic processes including the cleavage of caspase-3 and DNA fragmentation [ 36 ]. However, the underlying mechanism of cell death induced by LMWC exposure still requires further long-term experiments to confirm.…”

The Breast Tumor Microenvironment: Could Silicone Breast Implant Elicit Breast Carcinoma?

“…In HeLa cells (cervical carcinoma epithelial cells), toxicity was less efficient, whereas in HEp-2 cells (human epithelial cells), cell death was not observed. 36 The results presented in the article suggest that in addition to the mechanism proposed by our theory, the direct toxicity of silicone in T cells and eventually on epithelial cells in the TME could catalyze the process of oncogenesis.…”

“…In this context, in a recent study, Onneking et al described the possible cellular toxicity exerted by silicone. 36 According to the authors, silicone implants are composed of cross-linked alloys of polydimethylsiloxane chains in three-dimensional networks. Since the chains are cross-linked, lower molecular weight silicone particles with linear or cyclic structures, including D4, D5, and D6, filled the empty spaces.…”

Association of the BellaGel® Breast Implant Scandal with the Poly Implant Prothèse Fraud: A Review of Literatures

“…This was well evidenced by a post-mortem analysis of tissues sampled from a patient with a 17-year-history of gel bleed after receiving a silicone gel-filled breast implant. The patient was characterized by the presence of plaques or droplets containing silicones in several organs and nervous tissue [118]. Over the past decades, the involvement of a silicone gel-filled breast implant in the pathophysiology of autoimmune inflammatory disorders.…”