title: Genotoxicity of anti-tumor necrosis factor therapy in patients with juvenile idiopathic arthritis.
abstract: OBJECTIVE
  To assess the possible effects of both inflammation and the anti-tumor necrosis factor agents (anti-TNF) on DNA damage with a specific assay, and their effects on the repair capacity of DNA.
  
  
  METHODS
  From a group of 20 children with juvenile idiopathic arthritis (JIA), 16 patients who completed the study and 16 control subjects were evaluated. DNA damage and repair capacity were analyzed by the comet assay at the level of peripheral lymphocytes before anti-TNF (etanercept) injections and on the 15th, 90th, and 180th days after the first injection.
  
  
  RESULTS
  The amount of damage as detected by the aforementioned assay was higher in patients with JIA compared with controls. On the 15th day after the initial anti-TNF injection, there was a decrease in the mean DNA tail length of JIA patients, however on the 90th day an increase was observed; thereafter, an upward trend was observed until the end of the study. JIA patients had a DNA repair capacity that was significantly less than that of controls.
  
  
  CONCLUSIONS
  The results of the comet technique suggests that JIA patients already have increased basal DNA damage before anti-TNF therapy; they are more sensitive to the DNA damage produced by H(2)O(2), and have a less efficient DNA repair system in comparison with control cells. After an initial improvement at 2 weeks, parameters of genotoxicity worsened, and DNA repair was further impaired 6 months after the addition of an anti-TNF agent to treatment.
authors.affiliation: Hacettepe University Medical School, Ankara, Turkey. dottore_erkan@yahoo.com
authors.forename: Erkan
authors.initials: E
authors.lastname: Demirkaya
authors.forename: Ismet
authors.initials: I
authors.lastname: Cok
authors.forename: Emre
authors.initials: E
authors.lastname: Durmaz
authors.forename: Onur K
authors.initials: OK
authors.lastname: Ulutas
authors.forename: Nuray Aktay
authors.initials: NA
authors.lastname: Ayaz
authors.forename: Nesrin
authors.initials: N
authors.lastname: Besbas
authors.forename: Seza
authors.initials: S
authors.lastname: Ozen
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000494:pharmacology; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics*; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate