Metallic dental materials are frequently used in clinics. Cytotoxicity and allergy tests in vitro and in vivo have primarily been used to evaluate their safety. However, whether these dental materials cause genetic modifications leading to pathological conditions in oral tissues has not been shown. Gene mutations and epigenetic alterations are the initial steps of genetic modification. Environmental factors, including chemical components and mechanical stimulations, can cause epigenetic modifications that are often involved in pathogenic changes in humans. Therefore, we hypothesize that dental materials induce specific alterations in DNA methylation. This study aims to demonstrate specific alterations in DNA methylations in human gingival fibroblast cells (HGnF) induced by metal components (Ni and Ti ) of dental materials. The mRNA expression level of IL−6 for 2 weeks was significantly higher in the HGnF cells treated with 50 μM of Ni and 10 μM of Ti compared to the controls. Quantitative methylation − specific PCR ( qMSP) revealed that the DNA methylation percentage levels of IL−6 and IFN−γ in HGnF cells treated with 10 μM of Ti for 2 weeks were significantly lower compared to the controls. In conclusion, this study found hypomethylation of IL−6 and IFN−γ, followed by their upregulated expressions in HGnF cells stimulated with Ti. Methylation levels may serve as a new cytotoxic assessment tool, even for biocompatible materials.departmental bulletin pape
