Ethylene glycol dimethacrylate and diethylene glycol dimethacrylate exhibits cytotoxic and genotoxic effect on human gingival fibroblasts via induction of reactive oxygen species

Toxicol In Vitro. 2018 Mar:47:8-17. doi: 10.1016/j.tiv.2017.10.028. Epub 2017 Oct 28.

Abstract

Although methacrylic acid derivatives in their polymeric form are considered to be safe, insufficient polymerization and the release of monomers due to either mechanical or enzymatical factors can lead to their reaching millimolar concentrations in local tissue. The present study evaluates the effect of two methacrylate monomers - ethylene glycol dimethacrylate (EGDMA) and diethylene glycol dimethacrylate (DEGDMA) - on human gingival fibroblasts (HGFs). Both monomers were found to reduce cells viability in MTT assay, increase apoptosis and cause cell cycle arrest in G1/G0 phase. They also increased intracellular reactive oxygen species (ROS) production as measured by DCFH-DA and DHE probes and increased expression of GPx4 and SOD2. Both monomers increased DNA damage in comet assay. Moreover, HGFs were not able to repair those lesions within 120min of repair incubation. However, the monomers were not found to have any effect on the integrity of isolated plasmids. We postulate that EGDMA and DEGDMA exhibit their cytotoxic and genotoxic properties via increased production of ROS, which cause DNA damage, affect apoptosis, viability and cell cycle. Further studies are needed to better understand the properties of methacrylic acid monomers and to evaluate the risk that they cause for patients, dentists and dental technicians.

Keywords: Apoptosis; DNA damage; Diethylene glycol dimethacrylate; Ethylene glycol dimethacrylate; Human gingival fibroblasts; Reactive oxygen species.

Publication types

  • Comparative Study

MeSH terms

  • Apoptosis / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Comet Assay
  • Cross-Linking Reagents / toxicity*
  • DNA Damage
  • DNA Repair / drug effects*
  • Dental Materials / toxicity
  • Enzyme Induction / drug effects
  • Ethylene Glycols / toxicity*
  • G1 Phase / drug effects
  • Gingiva / cytology
  • Gingiva / drug effects*
  • Gingiva / metabolism
  • Glutathione Peroxidase / chemistry
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Humans
  • Methacrylates / toxicity*
  • Osmolar Concentration
  • Oxidative Stress / drug effects*
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Plasmids / drug effects
  • Reactive Oxygen Species / agonists
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / chemistry
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism

Substances

  • Cross-Linking Reagents
  • Dental Materials
  • Ethylene Glycols
  • Methacrylates
  • Reactive Oxygen Species
  • diethylene glycol dimethacrylate monomer
  • ethylene dimethacrylate
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • superoxide dismutase 2