Genotoxicity of anti-tumor necrosis factor therapy in patients with juvenile idiopathic arthritis.
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.
Demirkaya
Erkan
E
Hacettepe University Medical School, Ankara, Turkey. dottore_erkan@yahoo.com
Cok
Ismet
I
Durmaz
Emre
E
Ulutas
Onur K
OK
Ayaz
Nuray Aktay
NA
Besbas
Nesrin
N
Ozen
Seza
S
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*
D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate