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KMID : 0942820040030020063
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Journal of Korean Brain Tumor Society
2004 Volume.3 No. 2 p.63 ~ p.69
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Modulation of the Apoptosis in Radiotherapy
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Kang Shin-Hyuk
Chung Yong-Gu
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Abstract
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Multiple pathways are involved in maintaining the genetic integrity of a cell after its exposure to ionizing radiation. However, failure of these pathways results in cell death by inducing irreversible changes. Cellular injury of the radiation primarily leads to double-strand DNA breaks and DNA damage initiates signals that can ultimately activate either temporary checkpoints that permit time for genetic repair or irreversible growth arrest that results in cell death. One of the key proteins in the checkpoint pathways is the tumor suppressor gene p53, which coordinates DNA repair with cell cycle progression and apoptosis. Radiation also acts directly on the plasma membrane of several cell types, activating acid sphingomyelinase, which generates ceramide by enzymatic hydrolysis of sphingomyelin. Ceramide then acts as a secondary messenger in initiating an apoptotic response via the mitochondrial system. The numerous data are presented to show that in irradiated cells the balance between proapoptotic and antiapoptotic signaling may determine the apoptotic outcome in vitro and in vivo. An improved understanding of these signaling system may offer new opportunities for the modulation of radiation effects in the treatment of the human tumors.
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KEYWORD
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Irradiation, Double strand DNA breaks, P53, Cell membrane, Ceramide, Apoptosis
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