The Radioprotectors Amifostine and Sodium Selenite Do Not Modify the Radiosensitivity of Rat Rhabdomyosarcomas

Abstract

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/m²), sodium selenite (15 µg/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. Conclusion: 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.

Zone‐specific remodeling of tumor blood vessels affects tumor growth

“…To study the morphologic remodeling of tumor vessels in relation to local tumor growth we used rhabdomyosarcoma, which was grown for 20 days after implantation of the rhabdomyosarcoma cell line RH1 subcutaneously into the right flank of 9‐week‐old male adult WAG/RijH rats (mean body weight, 200 ± 20 g) as described previously 19, 20. Animals were fed a standard diet (atromin 1324, Altromin, Lage, Germany) and acidified vitamin C‐fortified water was given ad libitum.…”

“…However, it is still not sufficiently evaluated to what extent vascular stabilization and maturation take place in tumor and what the relation of these processes to tumor growth and metastasis is. To evaluate the relation between structural changes of tumor blood vessels and tumor growth we used the established experimental tumor model of rhabdomyosarcoma of the rat RH1 19, 20. To this aim we performed immunohistochemical, morphologic, and ultrastructural studies on tumor tissue enabling a zonal specific evaluation of the blood vessel structure in relation to the organization pattern of tumor cells and tumor necrosis.…”

Effects of Selenium on Radiation Responses of Tumor Cells and Tissue

“…This is particularly relevant for the one study, in a syngenic rat tumor, with clinically relevant, fractionated irradiation protocols [23]. However, only tumor growth delay, and not tumor cure was studied.…”

“…In a study in R1H rhabdomyosarkoma grown in WAG/ RijH rats [23], selenite was administered at a dose of 15 mg/kg 30 min before each of 30 fractions of 2 Gy given in 6 weeks. In this clinically relevant fractionation protocol, tumor growth delay and metastasis rate were not significantly changed.…”

Análise microscópica do efeito da radioterapia fracionada por cobalto-60 em mandíbula de rato

“…During the experimental period, the animals received Labinatype solid diet and water ad libitum and were randomly distributed into three groups: group 1 (experimental group 1) -15 animals submitted to 60 Gy radiationdose, and sacrificed at the end of the radiotherapy; group 2 (experimental group 2) -15 animals submitted to 60 Gy radiationdose, and sacrificed 30 days after the radiotherapy completion; group 3 (control group) -15 non-irradiated animals, subdivided into two groups with, respectively, seven rats for the experimental group 1 (group 3a), and eight for the experimental group 2 (group 3b). (16,17) . The distance between the radiation beam emitter and the animals skin surface was 60 cm ( Figure 1A).…”