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Chemoprevention by celecoxib and mutagen sensitivity of cyclin d1 in patients with oropharyngeal carcinoma.

AbstractUNLABELLED:
The head and neck region is one of the most important locations predisposed for tobacco-associated cancer. Chemoprevention might offer a chance to decrease the risk for this type of disease.
MATERIALS AND METHODS:
Mini-organ cultures (MOC) of macroscopically-healthy pharyngeal tissues from 20 patients with oropharyngeal squamous cell carcinoma (SCC) and from 20 controls were employed in the study. MOC were firstly incubated with Celecoxib, and DNA damage was induced by incubation with Benz[a]pyren-7,8-diol-9,10-epoxid (BPDE), a major representative of tobacco-associated carcinogens. DNA damage was evaluated with the alkaline single-cell microgel electrophoresis (Comet assay). Furthermore, fragmentation of the cyclin D1 gene, a gene of special importance in head and neck carcinogenesis was examined by the Comet-FISH assay. Finally, the chemoprotective potential of Celecoxib was analyzed after incubation with MOC.
RESULTS:
As expected, BPDE caused significant DNA fragmentation in tumor compared to negative control tissues. No enhanced damage was observed in the cyclin D1 gene. DNA fragmentation was significantly reduced when MOC were incubated with Celecoxib in the tumor group. Surprisingly, these effects were also observed in the group without cancer of the oropharynx, although COX-2 is not expressed in macroscopically-healthy mucosa.
CONCLUSION:
Celecoxib showed considerable chemoprotective effeciency against BPDE in both groups and this effect seems to be independent of COX-2 expression. No evidence for higher mutagen sensitivity in the Cyclin D1 gene was observed.
AuthorsMaximilian Reiter, Philipp Baumeister, Martina Hartmann, Sabina Schwenk-Zieger, Ulrich Harréus
JournalIn vivo (Athens, Greece) (In Vivo) 2014 Jan-Feb Vol. 28 Issue 1 Pg. 49-53 ISSN: 1791-7549 [Electronic] Greece
PMID24425835 (Publication Type: Journal Article)
Chemical References
  • Mutagens
  • Pyrazoles
  • Sulfonamides
  • Cyclin D1
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Celecoxib
Topics
  • Adult
  • Aged
  • Carcinoma, Squamous Cell (drug therapy, genetics, pathology)
  • Celecoxib
  • Chemoprevention
  • Cyclin D1 (metabolism)
  • Cyclooxygenase 2 (biosynthesis)
  • DNA Damage (drug effects)
  • DNA Fragmentation (drug effects)
  • Female
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Head and Neck Neoplasms (drug therapy, genetics, pathology)
  • Humans
  • Male
  • Middle Aged
  • Mutagens (toxicity)
  • Organ Culture Techniques
  • Oropharyngeal Neoplasms (drug therapy, genetics, pathology)
  • Pyrazoles (administration & dosage)
  • Sulfonamides (administration & dosage)
  • Tobacco Use Disorder (drug therapy, genetics, pathology)

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