title: Chemoprevention by celecoxib and mutagen sensitivity of cyclin d1 in patients with oropharyngeal carcinoma.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otorhinolaryngology/Head and Neck Surgery, Grosshadern Clinic, Ludwig Maximilians University, Marchioninistrasse 15, 81377 Munich, Germany. maximilian.reiter@med.uni-muenchen.de.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Reiter
authors.forename: Philipp
authors.initials: P
authors.lastname: Baumeister
authors.forename: Martina
authors.initials: M
authors.lastname: Hartmann
authors.forename: Sabina
authors.initials: S
authors.lastname: Schwenk-Zieger
authors.forename: Ulrich
authors.initials: U
authors.lastname: Harréus
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000068579:Celecoxib; D018890:Chemoprevention; D019938:Cyclin D1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004249:DNA Damage / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity; D009924:Organ Culture Techniques; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011720:Pyrazoles / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D014029:Tobacco Use Disorder / Q000188:drug therapy / Q000235:genetics / Q000473:pathology
chemical_list: D009153:Mutagens; D011720:Pyrazoles; D013449:Sulfonamides; D019938:Cyclin D1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib
keywords: BPDE; Celecoxib; Comet FISH; Comet assay; chemoprevention; cyclin D1; mutagen sensitivity