COX-2 inhibitors celecoxib and rofecoxib prevent oxidative DNA fragmentation.
BACKGROUND
Cyclooxygenase (COX) is the key regulatory enzyme in prostaglandin (PG) synthesis and is up-regulated in many premalignant and malignant lesions. The aim of this study was to investigate the in vitro DNA protective or damaging effects of COX-2 inhibitors using the single-cell gel electrophoresis (Comet) assay.


METHODS
Cells from miniorgan cultures of pharyngeal mucosa from 30 patients were incubated once or five times with the COX-2 inhibitors celecoxib and rofecoxib. After treatment with H2O2, DNA fragmentation was determined.


RESULTS
DNA strand-breaks were significantly reduced in cells pre-incubated with COX-2 inhibitors. Repeated incubation with celecoxib showed the strongest effect. This direct influence on DNA repair could be excluded by implementing DNA repair steps into the Comet assay.


CONCLUSIONS
The findings suggest that, in addition to the known influence of COX-2 inhibitors on immune surveillance, neo-angiogenesis and cell proliferation, these substances may express a direct antimutagenic effect in conditions of oxidative stress.
Matthias
Christoph
C
Clinical Experimental Oncology, ENT Department, Ludwig-Maximilians-University, Munich, Germany. christoph.matthias@med.uni-muenchen.de
Schuster
Marie Therese
MT
Zieger
Sabina
S
Harréus
Ulrich
U
D000068579:Celecoxib; D020552:Comet Assay; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology*; D007827:Laryngitis / Q000201:enzymology / Q000235:genetics; D007971:Leukoplakia / Q000201:enzymology / Q000235:genetics; D009061:Mouth Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010614:Pharynx / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D011230:Precancerous Conditions / Q000201:enzymology* / Q000235:genetics*; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D006861:Hydrogen Peroxide; D000068579:Celecoxib