Reduction of DNA damage by curcumin and celecoxib in epithelial cell cultures of the oropharynx after incubation with tobacco smoke condensate

摘要

Background: Tobacco smoke, as the major risk factor for the development of squamous cell cancer of the head and neck (HNSCC), contains various xenobiotics, such as polycyclic aromatic hydrocarbons, nitrosamines, aromatic amines and phenols. Chemoprevention either by artificial agents such as celecoxib, or natural compounds such as curcumin, might offer a chance to reduce the risk of developing malignant transformation. Materials and Methods: In order to evaluate the DNA-damaging effects of smoke condensate towards human mucosa cells of the oropharynx, mini organ cultures (MOC) of macroscopically healthy pharyngeal tissue of 40 patients with oropharyngeal SCC were used. After incubation with smoke condensate DNA damage was evaluated with the alkaline single-cell microgel electrophoresis (comet assay). The chemoprotective potential of curcumin and celecoxib was analyzed after their incubation with the condensate-treated MOCs. As DNA-damaging and chemopreventive effects might not be equally distributed over the whole DNA, fragmentation of the epithelial growth factor receptor (EGFR) gene was additionally examined by Comet fluorescence in situ hybridization (FISH). Results: As expected, tobacco smoke condensate caused significant DNA fragmentation compared to the negative control. No enhanced damage was observed on the EGFR gene. DNA fragmentation was significantly reduced when MOCs were incubated with celecoxib (p≤0.001) and with curcumin (p≤0.001). Conclusion: Both celecoxib and curcumin showed considerable chemoprotective effects towards the impact of smoke condensate. No evidence was found for higher susceptibility to damage in the EGFR gene.