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.

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