title: The role of DNA damage and caspase activation in cytotoxicity and genotoxicity of macrophages induced by bisphenol-A-glycidyldimethacrylate.
abstract: OBJECTIVE
  To evaluate the potential toxicological implications of BisGMA on murine macrophage cell line RAW264.7.
  
  
  METHODS
  Lactate dehydrogenase release, flow cytometry, Western blot and fluorometric assays were used to detect cell viability, mode of cell death and caspase activities, respectively. In addition, alkaline single-cell gel electrophoresis and cytokinesis-block micronucleus assays were applied to detect genotoxicity. Statistical analyses were performed using anova followed by the Bonferroni's t-test for multi-group comparisons test.
  
  
  RESULTS
  BisGMA demonstrated a cytotoxic effect on RAW264.7 cells in a dose-dependent and a time-dependent manner (P < 0.05). BisGMA was found to induce two modes of cell death. The mode of cell death changed from apoptosis to necrosis as the concentrations of BisGMA elevated. Caspase-3, caspase-8 and caspase-9 activities were significantly induced by BisGMA in a dose-dependent manner (P < 0.05). Moreover, BisGMA exhibited genotoxicity via a dose-related increase in the numbers of micronucleus and DNA strand breaks (P < 0.05).
  
  
  CONCLUSIONS
  Cytotoxicity and genotoxicity induced by BisGMA are mediated by DNA damage and caspase activation.
authors.affiliation: Department of Pharmacology, Chung Shan Medical University Department of Dentistry, Taiwan.
authors.forename: Y C
authors.initials: YC
authors.lastname: Li
authors.forename: Y H
authors.initials: YH
authors.lastname: Kuan
authors.forename: F M
authors.initials: FM
authors.lastname: Huang
authors.forename: Y C
authors.initials: YC
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017438:Bisphenol A-Glycidyl Methacrylate / Q000633:toxicity*; D015153:Blotting, Western; D053148:Caspase 3 / Q000187:drug effects; D053181:Caspase 8 / Q000187:drug effects; D053453:Caspase 9 / Q000187:drug effects; D020169:Caspases / Q000187:drug effects*; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D003603:Cytotoxins / Q000633:toxicity*; D004249:DNA Damage; D003764:Dental Materials / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000633:toxicity; D005434:Flow Cytometry; D005470:Fluorometry; D007770:L-Lactate Dehydrogenase / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D009336:Necrosis; D013997:Time Factors
chemical_list: D003603:Cytotoxins; D003764:Dental Materials; D020536:Enzyme Activators; D009153:Mutagens; D017438:Bisphenol A-Glycidyl Methacrylate; D007770:L-Lactate Dehydrogenase; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases