title: 8-prenylnaringenin and tamoxifen inhibit the shedding of irradiated epithelial cells and increase the latency period of radiation-induced oral mucositis : cell culture and murine model.
abstract: OBJECTIVE
  The major component in the pathogenesis of oral radiation-induced mucositis is progressive epithelial hypoplasia and eventual ulceration. Irradiation inhibits cell proliferation, while cell loss at the surface continues. We conceived to slow down this desquamation by increasing intercellular adhesion, regulated by the E-cadherin/catenin complex. We investigated if 8-prenylnaringenin (8-PN) or tamoxifen (TAM) decrease the shedding of irradiated human buccal epithelial cells in vitro and thus delay the ulcerative phase of radiation-induced mucositis in vivo.
  
  
  METHODS
  In vitro, aggregates of buccal epithelial cells were irradiated and cultured in suspension for 11 days. 8-PN or TAM were investigated regarding their effect on cell shedding. In vivo, the lower tongue surface of mice was irradiated with graded single doses of 25 kV X-rays. The incidence, latency, and duration of the resulting mucosal ulcerations were analyzed after topical treatment with 8-PN, TAM or solvent.
  
  
  RESULTS
  8-PN or TAM prevented the volume reduction of the irradiated cell aggregates during the incubation period. This was the result of a higher residual cell number in the treated versus the untreated irradiated aggregates. In vivo, topical treatment with 8-PN or TAM significantly increased the latency of mucositis from 10.9 to 12.1 and 12.4 days respectively, while the ulcer incidence was unchanged.
  
  
  CONCLUSIONS
  8-PN and TAM prevent volume reduction of irradiated cell aggregates in suspension culture. In the tongues of mice, these compounds increase the latency period. This suggests a role for these compounds for the amelioration of radiation-induced mucositis in the treatment of head and neck tumors.
authors.affiliation: Laboratory of Experimental Cancer Research, Department Radiation Oncology and Experimental Cancer Research, Ghent University, De Pintelaan 185 1P7, 9000, Ghent, Belgium, tine.deryck@ugent.be.
authors.forename: Tine
authors.initials: T
authors.lastname: De Ryck
authors.forename: Annouchka
authors.initials: A
authors.lastname: Van Impe
authors.forename: Barbara W
authors.initials: BW
authors.lastname: Vanhoecke
authors.forename: Arne
authors.initials: A
authors.lastname: Heyerick
authors.forename: Luc
authors.initials: L
authors.lastname: Vakaet
authors.forename: Wilfried
authors.initials: W
authors.lastname: De Neve
authors.forename: Doreen
authors.initials: D
authors.lastname: Müller
authors.forename: Margret
authors.initials: M
authors.lastname: Schmidt
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dörr
authors.forename: Marc E
authors.initials: ME
authors.lastname: Bracke
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects* / Q000528:radiation effects*; D002449:Cell Aggregation / Q000187:drug effects / Q000528:radiation effects; D002452:Cell Count; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D004847:Epithelial Cells / Q000187:drug effects* / Q000528:radiation effects*; D044950:Flavanones / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000473:pathology* / Q000517:prevention & control*; D013280:Stomatitis / Q000473:pathology* / Q000517:prevention & control*; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000528:radiation effects*
chemical_list: C119737:8-prenylnaringenin; D044950:Flavanones; D013629:Tamoxifen