Radiosensitization of a human soft tissue sarcoma cell line US8-93 (mt-p53) with the oxidizer sodium peroxodisulfate.
Side effects make it necessary to seek new radiosensitizers with low systemic actions. Sodium peroxodisulfate is a strong oxidizer classified as a safe agent with low systemic effects. We have examined the effect of this oxidizer on the radiosensitivity of the radioresistant human soft tissue sarcoma cell line US8-93 (mt-p53). The effects of peroxodisulfate (0.02-3.0 mM) with or without irradiation were studied by clonogenic survival assay, comet assay and the induction of apoptosis. We found sodium peroxodisulfate to be nontoxic for US8-93 up to a concentration of 0.1 mM. The combination of 0.1 mM sodium peroxodisulfate and irradiation showed a slight radiosensitizing effect with an enhancement factor of up to 1.5. This was coupled with an increase in apoptosis from 12 to 22% and an inhibition of repair of irradiation-induced DNA damage. Incubation with concentrations between 0.1-1.0 mM sodium peroxodisulfate resulted in a strong decrease of clonogenic survival with an IC50 of 0.28 mM. This was correlated with an increase in cross links. Furthermore, a strong additive effect was observed for the combination of 0.3 mM sodium peroxodisulfate and irradiation resulting in an increase in enhancement ratio from 1.3 at 2 Gy to 3.1 at 6 Gy (p</=0.08). However, no further increase in apoptosis was detected. Our results implicate sodium peroxodisulfate to be a potentially useful agent to improve the radiobiological efficacy in radioresistant soft tissue sarcomas as exemplified for the cell line US8-93.
Bache
Matthias
M
Department of Radiotherapy,Martin-Luther University of Halle-Wittenberg, Halle/Saale, Germany. matthias.bache@medizin.uni-halle.de
Dunst
Jürgen
J
Matschiner
Frank
F
Matschiner
Sybille
S
Kappler
Matthias
M
Bartel
Frank
F
Schmidt
Hannelore
H
Berghaus
Alexander
A
Taubert
Helge
H
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D020552:Comet Assay; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D009154:Mutation / Q000235:genetics; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012509:Sarcoma / Q000188:drug therapy / Q000532:radiotherapy*; D017670:Sodium Compounds / Q000494:pharmacology*; D013431:Sulfates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D011838:Radiation-Sensitizing Agents; D017670:Sodium Compounds; D013431:Sulfates; D016159:Tumor Suppressor Protein p53; C024625:sodium persulfate