title: Radiation-induced craniofacial bone growth inhibition: in vitro cytoprotection in the rabbit orbitozygomatic complex periosteum-derived cell culture.
abstract: BACKGROUND
  Radiotherapy for the management of head and neck cancer in pediatric patients results in severe inhibition of craniofacial bone growth. Previously, the infant rabbit orbitozygomatic complex was established as an experimental model. Amifostine, a cytoprotective agent, was found effective in preventing radiation-induced bone growth inhibition. This study was designed to investigate the effects radiation on osteogenic cells from infant rabbit orbitozygomatic complex periostea and to assess the effects of cytoprotection in vitro.
  
  
  METHODS
  Infant New Zealand White rabbits (n = 18) were randomized into three groups and received radiation (0, 10, or 15 Gy) to both orbitozygomatic complexes. Cell cultures were developed from orbitozygomatic complex periostea, and cell numbers, proliferation, alkaline phosphatase, and collagen type I expression and mineralization were assessed. Subsequently, rabbits (n = 18) were randomized into three groups to receive either radiation at the effective dose, pretreatment with amifostine (300 mg/kg, intravenously, 20 minutes before irradiation) with the effective radiation dose, or no treatment. Cell cultures were developed and tested for proliferation and alkaline phosphatase expression.
  
  
  RESULTS
  Irradiation resulted in a significant inhibition of cell numbers (p < 0.001) and proliferation (p < 0.01) at the 15-Gy dose and no statistically significant changes in alkaline phosphatase activity. Collagen type I expression and mineralization were also significantly reduced at the 15-Gy dose. Pretreatment with amifostine significantly (p < 0.05) enhanced the number of surviving cells.
  
  
  CONCLUSIONS
  Amifostine is capable of protecting orbitozygomatic complex periosteum-derived osteogenic cells from the deleterious effects of radiation. This study provides the basis for understanding the cellular mechanisms of radiation-induced craniofacial bone growth inhibition and cytoprotection by amifostine.
authors.affiliation: Toronto, Ontario, Canada; and Geneva, Switzerland From the Center for Craniofacial Care and Research, Division of Plastic Surgery, and the Research Institute, the Hospital for Sick Children; the Pediatric Surgery Clinic, University of Geneva Children's Hospital; the Samuel Lunenfeld Research Institute and Department of Pathology, Mount Sinai Hospital; the Department of Clinical Physics, Ontario Cancer Institute, Princess Margaret Hospital, University Health Network; and the Division of Plastic Surgery, University Health Network and University of Toronto.
authors.forename: Artur M
authors.initials: AM
authors.lastname: Gevorgyan
authors.forename: Giorgio C
authors.initials: GC
authors.lastname: La Scala
authors.forename: Balram
authors.initials: B
authors.lastname: Sukhu
authors.forename: Iona T
authors.initials: IT
authors.lastname: Leung
authors.forename: Homa
authors.initials: H
authors.lastname: Ashrafpour
authors.forename: Ivan
authors.initials: I
authors.lastname: Yeung
authors.forename: Peter C
authors.initials: PC
authors.lastname: Neligan
authors.forename: Cho Y
authors.initials: CY
authors.lastname: Pang
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Forrest
mesh_terms: D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D001846:Bone Development / Q000187:drug effects* / Q000528:radiation effects*; D002478:Cells, Cultured; D019610:Cytoprotection; D008297:Male; D023421:Models, Animal; D009915:Orbit / Q000187:drug effects / Q000528:radiation effects; D010006:Osteoblasts / Q000187:drug effects / Q000528:radiation effects; D010521:Periosteum / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D011817:Rabbits; D011833:Radiation Injuries, Experimental / Q000503:physiopathology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D015050:Zygoma / Q000187:drug effects / Q000528:radiation effects
chemical_list: D011837:Radiation-Protective Agents; D004999:Amifostine