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Mechanisms of radiation-induced craniofacial bone growth inhibition and possibilities of cytoprotection

Defense Thèse de privat-docent : Univ. Genève, 2012
Abstract Malignancies are frequently located in the head and neck region in children; their management usually requires radiotherapy, which has severe consequences on the growth of the craniofacial skeleton. The purpose of this work is to investigate the effects of radiation in the growing craniofacial skeleton in a rabbit model in vivo and in vitro and the possibilities of growth preservation using the cytoprotective drug Amifostine. The effects of radiation were studied in a single-dose radiation model, then in a more clinically-relevant fractionated-dose radiation model. Both radiation administration modes produced significant bone growth impairment. Administration of Amifostine prior to radiation significantly preserved craniofacial growth; this did not appeared to be related to vascularity as we did not demonstrated histomorphometric vessel changes or long-lasting changes in blood flow. Amifostine- treated animals had increased osteoblast counts, and improved bone turn-over compared to unprotected animals. In vitro, Amifostine enhanced the number of surviving cells after irradiation. This work suggests that radioprotection offers a viable pathway for the prevention of radiation-induced craniofacial bone growth inhibition and ensuing deformities.
Keywords AmifostineAmifostine/*pharmacologyAmifostine/pharmacology/*therapeutic useAnimalsBone DevelopmentBone Development/*drug effects/*radiation effectsCells, CulturedCephalometryCraniofacial bone growthCytoprotectionDose FractionationFacial Bone/growth and developmentFacial Bone/radiation effectsFacial Bones/drug effects/*growth & development/*radiation effectsGrowth/radiation effectsHead and Neck Neoplasms/radiotherapyHemodynamics/*radiation effectsHistologyHistopathologyMaleMandible/radiographyModels, AnimalOrbitOrbit/drug effects/radiation effectsOrbit/growth & development/radiation effects/radiographyOsteoblasts/drug effects/radiation effectsPeriosteum/cytology/drug effects/radiation effectsRabbitsRabbits/radiation effectsRadiationRadiation Injuries, Experimental/*physiopathologyRadiation protectionRadiation Protection/drug effectsRadiation-protective agentsRadiation-Protective Agents/*pharmacologyRadiation-Protective Agents/pharmacology/*therapeutic useRadiationRadiation InjuriesRadiation/adverse effectsRandom AllocationSkull/growth & development/radiation effectsSkull/growth and developmentTomography, X-Ray ComputedZygomaZygoma/drug effects/radiation effectsZygoma/growth & development/radiation effects/radiography
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LA SCALA, Giorgio. Mechanisms of radiation-induced craniofacial bone growth inhibition and possibilities of cytoprotection. Université de Genève. Thèse de privat-docent, 2012. doi: 10.13097/archive-ouverte/unige:21690 https://archive-ouverte.unige.ch/unige:21690

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Deposited on : 2012-06-27

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