title: DNA-damage, cell-cycle arrest and apoptosis induced in BEAS-2B cells by 2-hydroxyethyl methacrylate (HEMA).
abstract: The methacrylate monomer 2-hydroxyethyl methacrylate (HEMA) is commonly used in resin-based dental restorative materials. These materials are cured in situ and HEMA and other monomers have been identified in ambient air during dental surgery. In vitro studies have demonstrated a toxic potential of methacrylates, and concerns have been raised regarding possible health effects due to inhalation. In this study we have investigated the mechanisms of HEMA-induced toxicity in the human lung epithelial cell line BEAS-2B. Depletion of cellular glutathione (GSH) and an increased level of reactive oxygen species (ROS) were seen after 2h of exposure, but the levels were restored to control levels after 12h. After 24h, inhibited cell proliferation and apoptotic cell death were found. The results of the Comet assay and the observed phosphorylation of DNA-damage-associated signalling proteins including Chk2, H2AX, and p53 suggest that the toxicity of HEMA is mediated by DNA damage. Further, the antioxidant trolox did not counteract the HEMA-induced cell-cycle arrest, which indicates that the DNA damage is of non-oxidative origin.
authors.affiliation: University of Bergen, Faculty of Medicine and Dentistry, Department of Clinical Dentistry, PB 7804, 5020 Bergen, Norway. vea@niom.no
authors.forename: V
authors.initials: V
authors.lastname: Ansteinsson
authors.forename: A
authors.initials: A
authors.lastname: Solhaug
authors.forename: J T
authors.initials: JT
authors.lastname: Samuelsen
authors.forename: J A
authors.initials: JA
authors.lastname: Holme
authors.forename: J E
authors.initials: JE
authors.lastname: Dahl
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects*; D003764:Dental Materials / Q000633:toxicity*; D006801:Humans; D008689:Methacrylates / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D002839:Chromans; D003764:Dental Materials; D008689:Methacrylates; D017382:Reactive Oxygen Species; C005044:hydroxyethyl methacrylate; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid