title: Cell toxicity of methacrylate monomers-the role of glutathione adduct formation.
abstract: Polymer-based dental restorative materials are designed to polymerize in situ. However, the conversion of methacrylate monomer to polymer is never complete, and leakage of the monomer occurs. It has been shown that these monomers are toxic in vitro; hence concerns regarding exposure of patients and dental personnel have been raised. Different monomer methacrylates are thought to cause toxicity through similar mechanisms, and the sequestration of cellular glutathione (GSH) may be a key event. In this study we examined the commonly used monomer methacrylates, 2-hydroxyethylmethacrylate (HEMA), triethylenglycol-dimethacrylate (TEGDMA), bisphenol-A-glycidyl-dimethacrylate (BisGMA), glycerol-dimethacrylate (GDMA) and methyl-methacrylate (MMA). The study aimed to establish monomers' ability to complex with GSH, and relate this to cellular toxicity endpoints. Except for BisGMA, all the monomer methacrylates decreased the GSH levels both in cells and in a cell-free system. The spontaneous formation of methacrylate-GSH adducts were observed for all methacrylate monomers except BisGMA. However, we were not able to correlate GSH depletion and toxic response measured as SDH activity and changes in cell growth pattern. Together, the current study indicates mechanisms other than GSH-binding to be involved in the toxicity of methacrylate monomers.
authors.affiliation: Department of Clinical Dentistry, University of Bergen, Faculty of Medicine and Dentistry, Bergen, Norway; Nordic Institute of Dental Materials (NIOM), PO Box 3874 Ullevaal stadion, N-0805 Oslo, Norway.
authors.forename: V
authors.initials: V
authors.lastname: Ansteinsson
authors.forename: H B
authors.initials: HB
authors.lastname: Kopperud
authors.forename: E
authors.initials: E
authors.lastname: Morisbak
authors.forename: J T
authors.initials: JT
authors.lastname: Samuelsen
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002474:Cell-Free System; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D008689:Methacrylates / Q000737:chemistry / Q000633:toxicity*; D011108:Polymers / Q000737:chemistry / Q000633:toxicity; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D008689:Methacrylates; D011108:Polymers; D013385:Succinate Dehydrogenase; D005978:Glutathione
keywords: GSH; dental restorative materials; methacrylate monomers; oxidative stress; toxicity