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.