The Mechanism of Post-irradiation Hypertonic Treatment Induced Fixation of Potentially Lethal Damage in Glioma Cells

• Main Authors: Kuang-Yih Wang, 王光毅
• Other Authors: Jeng-Jong Hwang
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/09462504082627892589

碩士 === 國立陽明大學 === 放射醫學科學研究所 === 94 === The molecular mechanism underlying radiation potentially lethal damage (PLD) has been of great interest, yet remains unclear, in radiation biology for more than 30 years. In this study, we applied high-density oligonucleotide microarray and bioinformatics to investigate the hypertonic effect on PLD in U87MG glioma cells. Analysis of the microarray data showed that the expression levels of 210 genes out of 20,173 genes were altered. Classification of these affected 210 genes according to their biological functions indicated that they are involved in metabolism/energy, cell communication/signaling, transport, localization, response to stimuli, cell organization biogenesis, morphogenesis, immune response, cell cycle, neurophysiological process, cell proliferation and cell death. In addition, a unique set of mitochondrial genes responsible for ATP production including MTND1, MTND3, MTCO1, MTCO2 and MTATP8 were down-regulated. Inhibition of mitochondria transcription machinery and ATP exhaustion will affect cell's normal physiology and cause necrosis. Cell death through senescence was also observed. Such catastrophe action due to energy depletion following hypertonic treatment may explain not only the enhanced cell killing, but the inhibited repair protein mobility as well. Phosphorylated H2AX assay was also related with the increase of DNA double strand breaks (DSBs), which was consistent with the increased α component in the survival response curve. DNA histogram showed that the enhanced cell killing may depend on cell-cycle checkpoints. This investigation with systemic biology and high-throughput microarray may be helpful in elucidating molecular mechanism underlying PLD fixation.