The differential effects of the radioprotectant drugs amifostine and sodium selenite treatment in combination with radiation therapy on constituent bone cells, Ewing's sarcoma of bone tumor cells, and rhabdomyosarcoma tumor cells in vitro.
The purpose of this study was to determine the differential effects of therapeutic X-radiation on constituent bone cells relative to the pediatric tumor cells: Ewing's sarcoma of bone and rhabdomyosarcoma. In addition, the radioprotectant drugs amifostine and sodium selenite were administered to constituent bone cells and the two tumor cells to determine if the radioprotectants differentially protect bone cells while not benefiting the tumor cells. These studies are a necessary first step in determining the potential clinical benefit of radioprotective therapy. An established in vitro cell culture model employing both constituent bone cells (osteoblasts, primary bone marrow monocytes, osteoclasts chondrocytes, and endothelial cells) and the tumor cells lines (Ewing's sarcoma of bone and rhabdomyosarcoma) were exposed to irradiation, amifostine, and sodium selenite. Cells were then assayed for changes in cell number, cytotoxicity, mineralization, bone resorption, cell attachment, osteocalcin, caspase-3 expression, clonogenic survival, and alkaline phosphatase expression. Radiation therapy differentially decreased cell number; with osteoblasts being shown to be the least sensitive to irradiation, the tumor cells had an intermediate sensitivity and monocytes were the most sensitive. Both amifostine and sodium selenite protected chondrocytes and osteoblasts from the negative effects of irradiation, while not protecting the tumor cells. The pediatric tumor cell lines were generally more radiosensitive than the bone cells examined. The radioprotectant drugs amifostine and sodium selenite provided significant radioprotection to constituent bone cells while not protecting the tumor cells. Finally, amifostine and sodium selenite therapy provided an additional benefit beyond radioprotection by increasing cytotoxicity in nonirradiated and irradiated tumor cells.
Margulies
Bryan S
BS
Department of Orthopedic Surgery, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, New York 13210, USA. margulib@upstate.edu
Damron
Timothy A
TA
Allen
Matthew J
MJ
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004354:Drug Screening Assays, Antitumor; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D018038:Sodium Selenite / Q000494:pharmacology*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy
D011837:Radiation-Protective Agents; D018038:Sodium Selenite; D004999:Amifostine