Radioprotection of osteoblasts by a fractionated dose regimen and amifostine.
BACKGROUND
Radioprotective modalities such as dose fractionation and pharmacologic agents such as amifostine have been used to protect bone and other types of normal tissue from the damaging effects of ionizing radiation without significantly impacting tumor kill. To better understand the cellular mechanism of radioprotection of osseous tissue, the authors sought to determine the effect of dose fractionation and amifostine on isolated osteoblasts.


METHODS
Isolated primary rat calvarial osteoblasts were exposed to single or fractionated doses of ionizing radiation both with and without amifostine pretreatment. Endpoints included cell growth (n = 4), vascular endothelial growth factor production as measured by enzyme-linked immunosorbent assay (n = 3), and early osteodifferentiation as measured by a quantitative alkaline phosphatase assay (n = 3).


RESULTS
Both dose fractionation and amifostine protect osteoblasts from the growth inhibitory effects of ionizing radiation. Fractionation but not amifostine was protective for hypoxia-induced vascular endothelial growth factor production (used as a surrogate marker of normal osteoblast function). Neither fractionation nor amifostine could prevent the inhibitory effect of ionizing radiation on normal osteoblast osteodifferentiation as measured by alkaline phosphatase production.


CONCLUSIONS
Both dose fractionation and amifostine have valid roles as radioprotectants for osteoblasts and can act in an additive fashion. Radioprotection of cell growth and viability does not necessarily correlate with preservation of normal cellular function. Combination protocols involving dose fractionation and amifostine may be effective in radioprotection of osteoblasts and normal osseous tissue.
Wong
Alex K
AK
New York, N.Y. From the Plastic and Reconstructive Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center.
Mei
Lily
L
Soares
Marc A
MA
Schönmeyr
Björn H
BH
Mehrara
Babak J
BJ
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D011837:Radiation-Protective Agents; D042461:Vascular Endothelial Growth Factor A; D004999:Amifostine