Kariya Shinji, Sawada Ken, Kobayashi Toshihiro, Karashima Takashi, Shuin Taro, Nishioka Akihito, Ogawa Yasuhiro
Department of Diagnostic Radiology and Radiation Oncology, Kochi Medical School, Kochi, Japan.
Int J Radiat Oncol Biol Phys. 2009 Oct 1;75(2):449-54. doi: 10.1016/j.ijrobp.2009.04.092.
To study the effect of hydrogen peroxide (H(2)O(2)) on radiation-induced apoptosis in human prostate cancer PC-3 cells.
At 4h before the irradiation, PC-3 cells were exposed to 10mM ammonium chloride (NH(4)Cl) concentrations. Subsequently, cells were exposed to 0.1mM H(2)O(2) just before the irradiations, which were administered with 10-MV X-rays at doses of 10 Gy.
The percentage of apoptotic cells at 48 h after X-irradiation alone, H(2)O(2) alone, and combined X-irradiation and H(2)O(2) was 1.85%, 4.85%, and 28.4%, respectively. With use of combined X-irradiation and H(2)O(2), production of reactive oxygen species (ROS) occurred 4h after the irradiation. This resulted in lysosomal rupturing, mitochondrial fragmentation, and the release of cytochrome c into the cytoplasm from the mitochondria. In contrast, when cells were exposed to NH(4)Cl before the X-irradiation and H(2)O(2) administration, apoptosis was almost completely suppressed, ROS production did not occur, lysosomal rupture and mitochondrial fragmentation were blocked, and cytochrome c was not released.
Hydrogen peroxide strongly enhanced lysosome-dependent radiation-induced apoptosis in human prostate cancer PC-3 cells. A combined use of X-rays and H(2)O(2) can also injure the mitochondrial cytoplasmic organelles and lead to the production of ROS that in and of itself might possibly induce apoptosis.
研究过氧化氢(H₂O₂)对人前列腺癌PC-3细胞辐射诱导凋亡的影响。
在照射前4小时,将PC-3细胞暴露于10mM氯化铵(NH₄Cl)浓度下。随后,在照射前将细胞暴露于0.1mM H₂O₂,照射采用10MV X射线,剂量为10Gy。
单独X射线照射、单独H₂O₂处理以及X射线与H₂O₂联合处理后48小时的凋亡细胞百分比分别为1.85%、4.85%和28.4%。采用X射线与H₂O₂联合处理时,照射后4小时产生活性氧(ROS)。这导致溶酶体破裂、线粒体碎片化以及细胞色素c从线粒体释放到细胞质中。相反,当细胞在X射线照射和H₂O₂处理前暴露于NH₄Cl时,凋亡几乎完全被抑制,ROS产生未发生,溶酶体破裂和线粒体碎片化被阻断,细胞色素c未释放。
过氧化氢强烈增强人前列腺癌PC-3细胞中溶酶体依赖性辐射诱导的凋亡。X射线与H₂O₂联合使用也会损伤线粒体细胞质细胞器并导致ROS产生,而ROS本身可能诱导凋亡。