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

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.publishedVersio

Organic leachables from resinbased dental restorative : characterization by use of combined gas chromatographymass spectrometry

During the last decade resin-based dental restorative materials have replaced amalgam as the first choice dental filling material. Resin-based dental restorative materials are complex polymers containing a variety of monomers and filler particles, as well as initiators, activators, stabilizers, plasticizers and other additives. Several studies have shown that many of the ingredients are leaching from the materials, even after adequate polymerization. It is known from in vitro studies that some of the compounds in the resin-based materials have cytotoxic, genotoxic or estrogenic potential. Allergenic effects in patients and dental personnel have also been reported. The aim of this study was to identify and quantify substances released from various types of resin-based dental restorative materials. Specimens were polymerized according to protocols from the producers and submerged in different solvents. To characterize a maximum elution potential, ethanol was used as an immersion media. Furthermore, immersion in Ringer’s solution and saliva was used to mimic clinical elution conditions. A combined Gas Chromatography - Mass Spectrometry (GC-MS) technique was used for the identification and quantification of eluates. The majority of eluting substances from the polymeric matrix are organic substances with low molecular weight, which are well suited for analysis by GC-MS. Tailor-made internal standards for HEMA and TEGDMA were synthesized for the quantification procedure. We have identified and quantified a number of compounds from several materials. Significant differences regarding type and amount of leachables between the materials are observed

Airborne exposure to gaseous and particle-associated organic substances in resin-based dental materials during restorative procedures

Dental composite dust has been shown to act as a vehicle for methacrylates in vivo/in vitro. The objective of this study was to assess airborne exposure of dental personnel to gaseous and particle‐associated organic constituents from resin‐based dental materials in a simulated clinic. Sampling of total aerosol fractions and gaseous substances was performed by dental students carrying particle filters and gas sorbents attached to a personal pump during preclinical restorative procedures in phantom models (n = 13). Water from the phantoms was sampled. Organic substances were extracted from the sampled water, particle filters, and gas sorbents. Qualitative and quantitative analyses were performed by gas chromatography‐mass spectrometry (GC‐MS) and ultra‐high‐performance liquid chromatography‐mass spectrometry (UHPLC‐MS). The methacrylates 2‐hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA) and the additives camphorquinone (CQ), butylated hydroxytoluene (BHT), and ethyl 4‐(dimethylamino)benzoate (DMABEE), were quantified in the gas and particle fractions sampled. A positive‐control experiment was conducted. No methacrylates were detected in the gas or particle fractions sampled, whereas strong signals for methacrylates were detected in the positive controls, matching the analysis of the uncured material. In addition, TEGDMA and DMABEE were quantified in the sampled water. Airborne exposure to constituents in resin‐based dental materials was below the detection limit. However, the extent of exposure is probably dependent on the procedure, preventive measures, and type of materials used

Airborne exposure to gaseous and particle-associated organic substances in resin-based dental materials during restorative procedures

Dental composite dust has been shown to act as a vehicle for methacrylates in vivo/in vitro. The objective of this study was to assess airborne exposure of dental personnel to gaseous and particle‐associated organic constituents from resin‐based dental materials in a simulated clinic. Sampling of total aerosol fractions and gaseous substances was performed by dental students carrying particle filters and gas sorbents attached to a personal pump during preclinical restorative procedures in phantom models (n = 13). Water from the phantoms was sampled. Organic substances were extracted from the sampled water, particle filters, and gas sorbents. Qualitative and quantitative analyses were performed by gas chromatography‐mass spectrometry (GC‐MS) and ultra‐high‐performance liquid chromatography‐mass spectrometry (UHPLC‐MS). The methacrylates 2‐hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA) and the additives camphorquinone (CQ), butylated hydroxytoluene (BHT), and ethyl 4‐(dimethylamino)benzoate (DMABEE), were quantified in the gas and particle fractions sampled. A positive‐control experiment was conducted. No methacrylates were detected in the gas or particle fractions sampled, whereas strong signals for methacrylates were detected in the positive controls, matching the analysis of the uncured material. In addition, TEGDMA and DMABEE were quantified in the sampled water. Airborne exposure to constituents in resin‐based dental materials was below the detection limit. However, the extent of exposure is probably dependent on the procedure, preventive measures, and type of materials used

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

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