title: Cytotoxicity and terminal differentiation of human oral keratinocyte by indium ions from a silver-palladium-gold-indium dental alloy.
abstract: OBJECTIVE
  Dental alloys containing indium (In) have been used in dental restoration for two decades; however, no study has investigated the biological effects of In ions, which may be released in the oral cavity, on human oral keratinocytes. The objective of the present study was to investigate the biological effects of In ions on human oral keratinocyte after confirming their release from a silver-palladium-gold-indium (Ag-Pd-Au-In) dental alloy.
  
  
  METHODS
  As a corrosion assay, a static immersion tests were performed by detecting the released ions in the corrosion solution from the Ag-Pd-Au-In dental alloy using inductively coupled plasma atomic emission spectroscopy. The cytotoxicity and biological effects of In ions were then studied with In compounds in three human oral keratinocyte cell lines: immortalized human oral keratinocyte (IHOK), HSC-2, and SCC-15.
  
  
  RESULTS
  Higher concentrations of In and Cu ions were detected in Ag-Pd-Au-In (P<0.05) than in Ag-Pd-Au, and AgCl deposition occurred on the surface of Ag-Pd-Au-In after a 7-day corrosion test due to its low corrosion resistance. At high concentrations, In ions induced cytotoxicity; however, at low concentrations (∼0.8In(3+)mM), terminal differentiation was observed in human oral keratinocytes. Intracellular ROS was revealed to be a key component of In-induced terminal differentiation.
  
  
  CONCLUSIONS
  In ions were released from dental alloys containing In, and high concentrations of In ions resulted in cytotoxicity, whereas low concentrations induced the terminal differentiation of human oral keratinocytes via increased intracellular ROS. Therefore, dental alloys containing In must be biologically evaluated for their safe use.
authors.affiliation: Department and Research Institute of Dental Biomaterials and Bioengineering, College of Dentistry, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea; BK21 PLUS Project, College of Dentistry, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department and Research Institute of Dental Biomaterials and Bioengineering, College of Dentistry, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea; BK21 PLUS Project, College of Dentistry, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Seo
authors.affiliation: Department and Research Institute of Dental Biomaterials and Bioengineering, College of Dentistry, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Department and Research Institute of Dental Biomaterials and Bioengineering, College of Dentistry, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Om
authors.affiliation: Department and Research Institute of Dental Biomaterials and Bioengineering, College of Dentistry, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors.forename: Kwang-Mahn
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department and Research Institute of Dental Biomaterials and Bioengineering, College of Dentistry, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea; BK21 PLUS Project, College of Dentistry, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea. Electronic address: kimkn@yuhs.ac.
authors.forename: Kyoung-Nam
authors.initials: KN
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D003343:Corrosion; D003722:Dental Alloys / Q000737:chemistry*; D055664:Electrochemical Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006047:Gold Alloys / Q000737:chemistry; D006801:Humans; D007204:Indium / Q000737:chemistry; D007477:Ions; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D008422:Materials Testing; D010165:Palladium / Q000737:chemistry; D011498:Protein Precursors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000737:chemistry; D013054:Spectrophotometry, Atomic; D014961:X-Ray Diffraction
chemical_list: D003722:Dental Alloys; D005353:Fibronectins; D006047:Gold Alloys; D007477:Ions; D011498:Protein Precursors; D017382:Reactive Oxygen Species; D007204:Indium; D012834:Silver; D010165:Palladium; C032253:involucrin; D007633:Keratins; D066246:ErbB Receptors
keywords: Corrosion resistance; Cytotoxicity; Human oral keratinocytes; Indium ions; Silver–palladium–gold–indium dental alloy; Terminal differentiation