title: Cytotoxicity and genotoxicity of a low-shrinkage monomer and monoacylphosphine oxide photoinitiator: Comparative analyses of individual toxicity and combination effects in mixtures.
abstract: To compare cytotoxicity and genotoxicity of novel urethane-based monomer FIT-852 and monoacylphosphine oxide photoinitiator (Lucirin TPO) with conventional Bisphenol A-glycidyl-methacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA) monomers and camphorquinone (CQ)/amine photoinitiator system, respectively. Moreover, we quantified and analyzed the combinatorial effects of individual substances in resin-based mixtures concerning the nature of the combinatorial effects.
  
  
  
  Cytotoxic and genotoxic effects of BisGMA, FIT, TEGDMA, CQ, DMAEMA and TPO and their combined toxicity in four clinically relevant mixtures (FIT/TPO, FIT/CQ, BisGMA/TPO, BisGMA/CQ) were tested on human fetal lung fibroblasts MRC-5 using MTT and Comet assays. We assessed combination effects of monomers and photoinitiators on overall toxicity from the measured concentration-effect relationships. Combination index (CI) was calculated on the basis of the median-effect equation derived from the mass-action law principle.
  
  
  
  Individual substances showed decreasing cytotoxic effects in the following order: BisGMA>TPO>FIT>CQ>DMAEMA>TEGDMA. Experimental mixtures showed decreasing cytotoxic effects in the order BisGMA/TPO>BisGMA/CQ>FIT/CQ>FIT/TPO. FIT-based mixtures exhibited antagonistic cytotoxic effects between components while BisGMA-based mixtures demonstrated synergistic effects at ED50.TPO amplified both antagonistic and synergistic cytotoxic effects in mixtures. Pure substances showed genotoxicity in the following order: TPO>BisGMA>FIT>CQ>TEGDMA. We did not detect the genotoxic potential of DMAEMA. The rank of genotoxic concentrations of the mixtures was: BisGMA/TPO>BisGMA/CQ>FIT/CQ>FIT/TPO.
  
  
  
  Lower cytotoxicity and genotoxicity of FIT than BisGMA suggests its greater biocompatibility. Conversely, photoinitiator TPO was significantly more cytotoxic and genotoxic than both CQ and DMAEMA. CI values showed that components of FIT-based mixtures exhibit an antagonistic cytotoxic effect, while compontents of BisGMA-based mixtures show synergism.
authors.affiliation: University of Belgrade, School of Dental Medicine, DentalNet Research Group, Rankeova 4, Belgrade, Serbia; University of Belgrade, Institute of Nuclear Sciences "Vinča", P.O. Box 522, Belgrade, Serbia. Electronic address: dragica.manojlovic@stomf.bg.ac.rs.
authors.forename: Dragica
authors.initials: D
authors.lastname: Manojlovic
authors.affiliation: University of Belgrade, Institute of Nuclear Sciences "Vinča", P.O. Box 522, Belgrade, Serbia.
authors.forename: Miroslav D
authors.initials: MD
authors.lastname: Dramićanin
authors.affiliation: University of Belgrade, School of Dental Medicine, DentalNet Research Group, Rankeova 4, Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Miletic
authors.affiliation: University of Belgrade, Faculty of Biology, Center for genotoxicology and Ecogenotoxicology, Studentski trg 16, Belgrade, Serbia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Mitić-Ćulafić
authors.affiliation: University of Belgrade, Faculty of Biology, Center for genotoxicology and Ecogenotoxicology, Studentski trg 16, Belgrade, Serbia.
authors.forename: Bojana
authors.initials: B
authors.lastname: Jovanović
authors.affiliation: University of Belgrade, Faculty of Biology, Center for genotoxicology and Ecogenotoxicology, Studentski trg 16, Belgrade, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Nikolić
mesh_terms: D017438:Bisphenol A-Glycidyl Methacrylate / Q000633:toxicity; D003188:Composite Resins / Q000633:toxicity*; D005347:Fibroblasts; D006801:Humans; D008168:Lung / Q000166:cytology; D008422:Materials Testing; D008689:Methacrylates; D010087:Oxides; D011092:Polyethylene Glycols; D011109:Polymethacrylic Acids
chemical_list: D003188:Composite Resins; D008689:Methacrylates; D010087:Oxides; D011109:Polymethacrylic Acids; D011092:Polyethylene Glycols; D017438:Bisphenol A-Glycidyl Methacrylate
keywords: Combinatorial effect; Cytotoxicity; Genotoxicity; Monomer; Photoinitiator