Apoptotic-resistance of the human osteosarcoma cell line HS-Os-1 to irradiation is converted to apoptotic-susceptibility by hydrogen peroxide: a potent role of hydrogen peroxide as a new radiosensitizer.

In our previous study, we demonstrated that the radioresistance of the human osteosarcoma cell line HS-Os-1, was considered to arise, at least in part, from the low level of ROS formation following irradiation, which in turn may have resulted from the strong scavenging ability of the cells for free radicals, including hydroxyl radicals. Following the study, we found that addition of 1 or 10 mM hydrogen peroxide induced ROS formation, oxidative DNA damage, dysfunction of the mitochondrial membrane potential, and early apoptotic changes in the human osteosarcoma cell line HS-Os-1. We therefore speculated that combined use of irradiation and hydrogen peroxide might exert an additive effect for apoptotic-resistant tumors such as the human osteosarcoma cell line HS-Os-1, in terms of preservation of the radiation-induced hydroxyl radical production supported by the intracellular ROS formation that is induced by exogenous hydrogen peroxide addition. Therefore, in this study, we examined the effect of various doses of irradiation on the existence of 0.1 mM hydrogen peroxide in the culture medium. We found that irradiation with 10 or 20 Gy, under the condition of the presence of 0.1 mM hydrogen peroxide, induced ROS formation, oxidative DNA damage, dysfunction of the mitochondrial membrane potential, and early apoptotic changes in the human osteosarcoma cell line HS-Os-1, though ROS formation and oxidative DNA damage were scarcely seen in response to irradiation of up to 30 Gy, as was shown in our previous study. We therefore concluded that the combined modality of irradiation and such a low concentration of hydrogen peroxide (0.1 mM) is potentially applicable in clinical radiotherapy for many kinds of apoptotic-resistant neoplasms in terms of achieving both local control and improving survival benefit of patients.