Dose‐ and time‐dependent effects of triethylene glycol dimethacrylate on the proteome of human THP‐1 monocytes

Abstract

Triethylene glycol dimethacrylate (TEGDMA) is commonly used in polymer resin-based dental materials. This study investigated the molecular mechanisms of TEGDMA toxicity by identifying its time- and dose-dependent effects on the proteome of human THP-1 monocytes. The effects of different concentrations (0.07-5 mM) and exposure times (0-72 h) of TEGDMA on cell viability, proliferation, and morphology were determined using a real-time viability assay, automated cell counting, and electron microscopy, and laid the fundament for choice of exposure scenarios in the proteomic experiments. Solvents were not used, as TEGDMA is soluble in cell culture medium (determined by photon correlation spectroscopy). Cells were metabolically labeled [using the stable isotope labeled amino acids in cell culture (SILAC) strategy], and exposed to 0, 0.3 or 2.5 mM TEGDMA for 6 or 16 h before liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses. Regulated proteins were analyzed in the STRING database. Cells exposed to 0.3 mM TEGDMA showed increased viability and time-dependent upregulation of proteins associated with stress/oxidative stress, autophagy, and cytoprotective functions. Cells exposed to 2.5 mM TEGDMA showed diminished viability and a protein expression profile associated with oxidative stress, DNA damage, mitochondrial dysfunction, and cell cycle inhibition. Altered expression of immune genes was observed in both groups. The study provides novel knowledge about TEGDMA toxicity at the proteomic level. Of note, even low doses of TEGDMA induced a substantial cellular response.

Analysis of Resin-Based Dental Materials’ Composition Depending on Their Clinical Applications

“…Some authors demonstrated adverse effects depending on the presence of TEGDMA, HEMA, or UDMA [ 32 , 33 , 34 , 35 , 36 , 37 ]. UDMA is a monomer commonly added in dental resin-based dental materials to enhance their viscosity and is considered an alternative to BisGMA in these materials [ 1 , 2 ].…”

“…Furthermore, the higher the degree of polymerization is, the less toxic the biological effects observed would be [10,12]. Some authors demonstrated adverse effects depending on the presence of TEGDMA, HEMA, or UDMA [32][33][34][35][36][37]. UDMA is a monomer commonly added in dental resin-based dental materials to enhance their viscosity and is considered an alternative to BisGMA in these materials [1,2].…”

Cytotoxicity of Methacrylate Dental Resins to Human Gingival Fibroblasts

“…Relatively high cytotoxicity of C was not linked to relevant growth inhibition, while E, and to a lesser extent F, exerted significant antiproliferative effects, but only limited cytotoxicity. Antiproliferative action of methacrylates was also described in human gingival fibroblasts [ 32 , 33 , 34 ], and this effect should be taken into account while testing resin cytotoxicity in cell lines. Published data emphasize inconsistent results of MTT and LDH-release tests in experiments of resin cytotoxicity in human gingival fibroblasts.…”

Influence of TEGDMA monomer on MMP-2, MMP-8, and MMP-9 production and collagenase activity in pulp cells

“…In this experimental design, pulp cells were exposed to 0.1, 0.2, and 0.75 mM TEGDMA solution for 24 h. Exposure time and concentrations were chosen due to the substantial cell death which was seen for all treated populations after 48 h and above concentrations of 0.75 mM in our pilot studies. Regarding the employed concentration and study time-frame, similar exposure conditions were used also in other studies to detect gene expression changes and production of specific proteins, all of which yielded representative findings [ 28 , 35 ].…”