IntroductionOn extrusion, endodontic sealers might come into close contact with the periapical tissues for long periods. The objective of this study was to test possible mutagenicity of resin-based endodontic sealers by evaluating their potential to induce DNA double-strand breaks (DSBs). MethodsHuman gingival fibroblasts were exposed to subtoxic concentrations of eluates from 1 epoxy resin–based endodontic sealer (AH Plus Jet) and 2 methacrylate-based endodontic sealers (EndoRez and Real Seal). As control, Calcicur, a Ca(OH)2-based sealer, was used. The γ-H2AX immunofluorescence assay was used to microscopically detect DNA DSBs, and a custom algorithm was developed to quantify them. ResultsThe cytotoxicity of the 24-hour eluates could be ranked in the following order: AH Plus Jet > Real Seal > EndoRez >> Calcicur. The γ-H2AX assay revealed that 1.3%–4.3% of the cell nucleus was occupied by foci when the cells were exposed to the eluates of the endodontic sealers. This was not significantly different from the negative control group in which the cells had been exposed to medium (2.1%). ConclusionsNo indications for increased risk of genotoxicity of resin-based root canal sealers caused by the induction of DNA DSBs were found in this study.