RT Journal Article SR Electronic T1 Type of Cell Death Induced by Seven Metals in Cultured Mouse Osteoblastic Cells JF In Vivo JO In Vivo FD International Institute of Anticancer Research SP 507 OP 512 VO 24 IS 4 A1 RENÉ GARCÍA CONTRERAS A1 JOSÉ ROGELIO SCOUGALL VILCHIS A1 HIROSHI SAKAGAMI A1 YUKO NAKAMURA A1 YUKIO NAKAMURA A1 YASUSHI HIBINO A1 HIROSHI NAKAJIMA A1 JUN SHIMADA YR 2010 UL http://iv.iiarjournals.org/content/24/4/507.abstract AB 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. α-MEM was used as a culture medium, since this medium provided much superior proliferation of MC3T3-E1 cells over DMEM. Ag (NH3)2F was the most cytotoxic, followed by CuCl>CuCl2 >CoCl2, NiCl2>FeCl3 and FeCl2 (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 (NH3)2F, CuCl, CoCl2 or NiCl2 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.