title: Type of cell death induced by seven metals in cultured mouse osteoblastic cells.
abstract: The use of dental metal alloys in the daily clinic makes it necessary to evaluate the cytotoxicity of eluted metal components against oral cells. However, the cytotoxic mechanism and the type of cell death induced by dental metals in osteoblasts have not been well characterized. This study investigated the cytotoxicity of seven metals against the mouse osteoblastic cell line MC3T3-E1. alpha-MEM was used as a culture medium, since this medium provided much superior proliferation of MC3T3-E1 cells over DMEM. Ag (NH(3))(2)F was the most cytotoxic, followed by CuCl>CuCl(2) >CoCl(2), NiCl(2)>FeCl(3) and FeCl(2) (least toxic). None of the metals showed any apparent growth stimulating effect (so-called 'hormesis') at lower concentrations. A time course study demonstrated that two hours of contact between oral cells and Ag (NH(3))(2)F, CuCl, CoCl(2) or NiCl(2) induced irreversible cell death. Contact with these metals induced a smear pattern of DNA fragmentation without activation of caspase-3. Preincubation of MC3T3-E1 cells with either a caspase inhibitor (Z-VAD-FMK) or autophagy inhibitors (3-methyladenine, bafilomycin) failed to rescue them from metal cytotoxicity. These data suggest the induction of necrotic cell death rather than apoptosis and autophagy by metals in this osteoblastic cell line.
authors.affiliation: Department of Orthodontics, Dental Research Center (CIEAO), Faculty of Dentistry, Autonomous University of State of México (UAEM), Toluca, Mexico.
authors.forename: René García
authors.initials: RG
authors.lastname: Contreras
authors.forename: José Rogelio Scougall
authors.initials: JR
authors.lastname: Vilchis
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hibino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
authors.forename: Jun
authors.initials: J
authors.lastname: Shimada
mesh_terms: D016475:3T3 Cells / Q000166:cytology / Q000187:drug effects; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D002712:Chlorides / Q000627:therapeutic use; D003035:Cobalt / Q000633:toxicity; D003300:Copper / Q000633:toxicity; D003470:Culture Media; D053938:DNA Fragmentation / Q000187:drug effects; D005290:Ferric Compounds / Q000627:therapeutic use; D007700:Kinetics; D008670:Metals / Q000633:toxicity*; D051379:Mice; D009532:Nickel / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects
chemical_list: D002712:Chlorides; D003470:Culture Media; D005290:Ferric Compounds; D008670:Metals; D003035:Cobalt; C022838:nickel chloride; D003300:Copper; D009532:Nickel; C018021:cobaltous chloride; C029892:cupric chloride; C024555:ferric chloride