Radiation-induced craniofacial bone growth inhibition: Investigation of the mechanisms and radioprotection in vitro

In this work, the cellular and functional mechanisms of radiation effects with and without radioprotection were investigated in cultured craniofacial osteoblast-like cells in order to understand the pathophysiology of radiation-induced craniofacial bone growth inhibition.; Primary periosteal osteoblast-like cells were obtained from the infant rabbit orbitozygomatic complex following radiation with or without intravenous Amifostine. MC3T3-E1 mouse calvarial osteoblastic cells underwent gamma-radiation with and without WR-2721 or WR-1065 (10-3-10-7 M, 30 minutes before radiation). Survival, viability and osteoblast phenotype were assessed.; Radiation resulted in a dose-dependent inhibition of survival and two-fold changes in osteoblast-like phenotype. Pre-treatment with Amifostine or WR-1065 (in primary and clonal cells, respectively) resulted in a significantly improved survival at clinically relevant radiation doses and drug concentrations.; This work establishes that Amifostine affords significant radioprotection of craniofacial osteoblast-like cells. This is important in devising pharmacological strategies for preventing impaired cramofacial bone growth in the survivors of head and neck cancer.