The radioprotectors amifostine and sodium selenite do not modify the radiosensitivity of rat rhabdomyosarcomas.
BACKGROUND
Radiotherapy of head and neck tumors often leads to acute reactions of the adjacent normal tissues resulting e.g. in mucositis and xerostomia. Therefore, radioprotective drugs have been developed to reduce these effects. Studies on a tumor model using amifostine and sodium selenite adjuvant to fractionated irradiation should show whether the radioprotective effect on normal tissue leads to an increase of radioresistance in the tumor and its metastatic potential.


METHODS
Rhabdomyosarcomas R1H of the rat growing subcutaneously in the right flank of male adult WAG/RijH rats were irradiated with 60Co-gamma rays (60 Gy/30 fractions/6 weeks). Amifostine (375 mg/m(2)), sodium selenite (15 microg/kg), and equivalent volumes of 0.9% saline were administered intraperitoneally 30 min before each irradiation. Tumor response was determined. Statistical analysis was performed using the post-hoc-test.


RESULTS
Irradiation alone inhibited R1H tumor growth (AUC 86.8+/-18.3). The efficacy of irradiation during radiotherapy was significantly improved by amifostine (AUC 63.1+/-15.8) in comparison to the irradiated controls. The radiosensitizing effect of sodium selenite (AUC 73.6+/-21.3) as well as irradiation and amifostine plus sodium selenite (AUC 68.3+/-7.8) was less compared to the irradiated controls and not statistically significant. However, tumor growth delay and metastasis rate were not changed by the radioprotective drugs. Further, the administration of amifostine and amifostine plus sodium selenite induced an enhanced decrease of animal body weight except for sodium selenite in comparison to the controls.


CONCLUSIONS
The application of amifostine and sodium selenite to conventionally fractionated irradiation have no influence on the radiosensitivity of the rhabdomyosarcoma R1H. The systemic toxicity of amifostine might be of importance for the radiation treatment of a patient.
Department of Oto-Rhino-Laryngology, University Hospital Hamburg-Eppendorf, Germany. sagowski@uke.uni-hamburg.de
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Sagowski
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Tesche
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Zywietz
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Wenzel
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Metternich
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D019583:Dose Fractionation, Radiation; D007274:Injections, Intraperitoneal; D008297:Male; D009368:Neoplasm Transplantation; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011867:Radioisotope Teletherapy; D051381:Rats; D011919:Rats, Inbred Strains; D012208:Rhabdomyosarcoma / Q000473:pathology / Q000532:radiotherapy*; D018038:Sodium Selenite / Q000494:pharmacology*; D012983:Soft Tissue Neoplasms / Q000473:pathology / Q000532:radiotherapy*
D003037:Cobalt Radioisotopes; D011837:Radiation-Protective Agents; D018038:Sodium Selenite; D004999:Amifostine