Ogawa Yasuhiro, Takahashi Toshiaki, Kobayashi Toshihiro, Kariya Shinji, Nishioka Akihito, Ohnishi Takenao, Saibara Toshiji, Hamasato Shinji, Tani Toshikazu, Seguchi Harumichi, Yoshida Shoji, Sonobe Hiroshi
Department of Radiology, Kochi Medical School, Oko-cho, Nankoku-shi, Kochi-Prefecture 783-8505, Japan.
Int J Mol Med. 2003 Dec;12(6):845-50.
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.
在我们之前的研究中，我们证明了人骨肉瘤细胞系HS-Os-1的辐射抗性，至少部分是由于照射后ROS生成水平较低，这反过来可能是由于细胞对包括羟基自由基在内的自由基具有较强的清除能力。在该研究之后，我们发现添加1或10 mM过氧化氢会诱导人骨肉瘤细胞系HS-Os-1产生ROS、氧化性DNA损伤、线粒体膜电位功能障碍和早期凋亡变化。因此，我们推测，对于诸如人骨肉瘤细胞系HS-Os-1这种抗凋亡肿瘤，联合使用照射和过氧化氢可能会产生相加效应，这是基于外源性添加过氧化氢诱导细胞内ROS生成，从而维持辐射诱导的羟基自由基产生。因此，在本研究中，我们检测了不同剂量照射对培养基中0.1 mM过氧化氢存在情况下的影响。我们发现，在存在0.1 mM过氧化氢的条件下，用10或20 Gy照射会诱导人骨肉瘤细胞系HS-Os-1产生ROS、氧化性DNA损伤、线粒体膜电位功能障碍和早期凋亡变化，不过如我们之前的研究所显示，照射高达30 Gy时几乎未见ROS生成和氧化性DNA损伤。因此，我们得出结论，照射与如此低浓度的过氧化氢（0.1 mM）联合应用，在实现局部控制和提高患者生存获益方面，对于多种抗凋亡肿瘤在临床放射治疗中可能具有潜在应用价值。
