title: Genotoxic and cytotoxic effects and gene expression changes induced by fixed orthodontic appliances in oral mucosa cells of patients: a systematic review.
abstract: BACKGROUND
  The accumulation of chronic or severe acute DNA and cellular damage in oral mucosa cells is one of the main factors that help initiate a wide range of malignant lesions in the oral cavity. There has been considerable controversy in the literature about the effect of such sustained genotoxic and cytotoxic damage to oral mucosa cells.
  
  
  OBJECTIVE
  The aim of this systematic review, reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, is to investigate the effects of such interventions.
  
  
  METHODS
  Electronic and manual searches were performed (15 May 2015) for Randomized Clinical Trials/quasi-Randomized Clinical Trials that analyzed the genotoxic/cytotoxic effects of these types of oral appliances in humans. A primary outcome (cell/DNA damage) and a number of secondary outcomes were examined. Two reviewers carried out the study selection and performed a "risk of bias" assessment [Cochrane Collaboration's tool]. Wherever possible the meta-analysis was conducted on homogenous groups.
  
  
  RESULTS
  From the electronic search (2797), 6 studies met the eligibility criteria. Most studies (5/6) observed significant differences in most comparisons at the short-term (1-3 months) and long-term (24-48 months) evaluations, with respect to critically acute genotoxic/cytotoxic effects. Some of the studies (2/3) concluded that the post-removable effects at DNA/cellular levels were not significant (p > 0.05) with respect to the controls.
  
  
  CONCLUSIONS
  Acute DNA/cellular damage in oral mucosa cells is induced by orthodontic appliances. Nevertheless, even though these effects were no longer detected after removing the appliances, more rigorous RCTs are needed to explore the extent to which acquired damage can be observed in the oral mucosa.
authors.affiliation: a Department of Stomatology , School of Dentistry, University of Seville , Seville , Spain .
authors.forename: Ana
authors.initials: A
authors.lastname: Martín-Cameán
authors.affiliation: b Area of Toxicology, Faculty of Pharmacy , University of Seville , Seville , Spain , and.
authors.forename: Angeles
authors.initials: A
authors.lastname: Jos
authors.affiliation: b Area of Toxicology, Faculty of Pharmacy , University of Seville , Seville , Spain , and.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Cameán
authors.affiliation: a Department of Stomatology , School of Dentistry, University of Seville , Seville , Spain .
authors.forename: Enrique
authors.initials: E
authors.lastname: Solano
authors.affiliation: c Department of Stomatology IV , School of Dentistry, Complutense University of Madrid , Madrid , Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Iglesias-Linares
mesh_terms: D004249:DNA Damage; D003764:Dental Materials / Q000009:adverse effects*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008670:Metals / Q000009:adverse effects*; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009967:Orthodontic Appliances / Q000009:adverse effects*; D018570:Risk Assessment; D013997:Time Factors
chemical_list: D003764:Dental Materials; D008670:Metals
keywords: Cytotoxicity; DNA damage; genotoxicity; metal release; oral mucosa; orthodontic appliance