title: Methacryloxylethyl Cetyl Ammonium Chloride Induces DNA Damage and Apoptosis in Human Dental Pulp Cells via Generation of Oxidative Stress.
abstract: The polymerizable antibacterial monomer methacryloxylethyl cetyl ammonium chloride (DMAE-CB) has provided an effective strategy to combat dental caries. However, the application of such material raises the question about the biological safety and the question remains open. The mechanism of this toxic action, however, is not yet clearly understood. The present study aims at providing novel insight into the possible causal link between cellular oxidative stress and DNA damage, as well as apoptosis in human dental pulp cells exposed to DMAE-CB. The enhanced formation of reactive oxygen species and depletion of glutathione, as well as differential changes in activities of superoxide dismutase, glutathione peroxidase, and catalase in DMAE-CB-treated cells indicated oxidative stress. By using substances that can alter GSH synthesis, we found that GSH was the key component in the regulation of cell response towards oxidative stress induced by DMAE-CB. The increase in oxidative stress-sensitive 8-Oxo-2'-deoxyguanosine (8-OHdG) content, formation of γ-H2AX and cell cycle G1 phase arrest indicated that DNA damage occurred as a result of the interaction between DNA base and ROS beyond the capacities of antioxidant mechanisms in cells exposed to DMAE-CB. Such oxidative DNA damage thus triggers the activation of ataxia telangiectasia-mutated (ATM) signaling, the intrinsic apoptotic pathway, and destruction of mitochondrial morphology and function.
authors.affiliation: 1. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: 1. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Sai
authors.initials: S
authors.lastname: Ma
authors.affiliation: 2. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Yirong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 3. Department of Orthopaedic Oncology, Xijing Hospital, the Fourth Military Medical University, Xi'an, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: 4. Department of Orthopaedic Surgery, Tangdu hospital, the Fourth Military Medical University, Xi'an, PR China.
authors.forename: Lequn
authors.initials: L
authors.lastname: Shan
authors.affiliation: 1. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Sun
authors.affiliation: 1. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D003782:Dental Pulp / Q000166:cytology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008689:Methacrylates / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D008689:Methacrylates; D000644:Quaternary Ammonium Compounds; D017382:Reactive Oxygen Species; C540902:methacryloxylethyl cetyl dimethyl ammonium; D005978:Glutathione
keywords: DNA damage; apoptosis; methacryloxylethyl cetyl ammonium chloride; mitochondria.; oxidative stress