title: Genotoxic effects of camphorquinone and DMT on human oral and intestinal cells.
abstract: OBJECTIVE
  Released components of oral biomaterials can leach into the oral cavity and may subsequently reach the gastrointestinal tract. Camphorquinone (CQ) is the most common used photoinitiator in resinous restorative materials and is often combined with the co-initiator N,N-dimethyl-p-toluidine (DMT). It has been shown that CQ exerts cytotoxic effects, at least partially due to the generation of reactive oxygen species (ROS). Objective of this study was to examine the cytotoxic and genotoxic potential of CQ in human oral keratinocytes (OKF6/TERT2) and immortalized epithelial colorectal adenocarcinoma cells (Caco-2). Furthermore, the effects of visible-light irradiation and the co-initiator DMT were investigated as well as the generation of ROS, the potential protective effect of glutathione (GSH) and a recovery period of CQ-treated Caco-2 cells.
  
  
  METHODS
  The alkaline comet assay was used to determine DNA damage. Additionally, an enzyme modified comet assay was applied, which detects 7,8-dihydro-8-oxoguanine (8-oxoguanine), a reliable marker for oxidative stress.
  
  
  RESULTS
  Our data revealed that high concentrations of CQ induced DNA lesions in OKF6/TERT2 cells. This DNA damage is at least partly caused by the generation of 8-oxoguanine. In addition, CQ and DMT increased ROS formation and induced DNA damage in Caco-2 cells. CQ-treatment resulted in generation of 8-oxoguanine. The antioxidant GSH efficiently prevented CQ-associated DNA damage. Furthermore, a recovery following CQ-treatment significantly reduced DNA damage.
  
  
  CONCLUSIONS
  We conclude that CQ-induced DNA damage is caused by oxidative stress in oral and intestinal cells. These lesions can be prevented and possibly repaired by GSH-treatment and recovery of cells after the photoinitiator is removed from cultures.
authors.affiliation: Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address: wessels.miriam@mh-hannover.de.
authors.forename: Miriam
authors.initials: M
authors.lastname: Wessels
authors.affiliation: Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Rimkus
authors.affiliation: Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Leyhausen
authors.affiliation: Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Volk
authors.affiliation: Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Geurtsen
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D018938:Caco-2 Cells / Q000187:drug effects*; D002164:Camphor / Q000031:analogs & derivatives* / Q000633:toxicity; D020552:Comet Assay; D004249:DNA Damage; D005978:Glutathione / Q000494:pharmacology*; D006147:Guanine / Q000031:analogs & derivatives / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000187:drug effects*; D009061:Mouth Mucosa / Q000166:cytology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000633:toxicity; D014052:Toluidines / Q000633:toxicity*
chemical_list: C453560:7,8-dihydro-8-oxoguanine; D000975:Antioxidants; D017382:Reactive Oxygen Species; D014052:Toluidines; D006147:Guanine; D002164:Camphor; D005978:Glutathione; C553149:camphorquinone; C015835:dimethyl-4-toluidine
keywords: 8-Oxoguanine; Camphorquinone; DNA damage; Reactive oxygen species