• Title/Summary/Keyword: Irreversible degradation

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Induction of G1 Phase Cell Cycle Arrest and Apoptotic Cell Death by 5-Fluorouracil in Ewing′s Sarcoma CHP-100 Cells (CHP-100 Ewing′s 육종세포에서 5-fluorouracil에 의한 G1 arrest 유도 및 apoptosis 유발에 관한 연구)

  • Kim, Sung Ok;Choi, Yung Hyun
    • Journal of Life Science
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    • v.26 no.9
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    • pp.1015-1021
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    • 2016
  • 5-fluorouracil (5-FU), a pyrimidine analog, is a widely used anticancer drug, which works through irreversible inhibition of thymidylate synthase. In the present study, it was investigated the anti-proliferative effects and molecular mechanisms of 5-FU using Ewing's Sarcoma CHP-100 Cells. The present data indicated that treatment of 5-FU to CHP-100 cells induced a G1 phase arrest of the cell cycle in a time-dependent manner. 5-FU-induced G1 arrest was correlated with the accumulation of the hypophosphorylated form of the retinoblastoma protein (pRB) and association of pRB with the transcription factors E2F-1 and E2F-4. Although 5-FU treatment did affect the levels of cyclin-dependent kinases, the levels of cyclin A and B were markedly down-regulated as compared with the untreated control group. In addition, 5-FU-induced G1 arrest of CHP-100 cells was also associated with the induction of apoptosis, as determined by apoptotic cell morphologies, degradation of poly(ADP-ribose) polymerase and Annexin V staining. Furthermore, 5-FU induced the loss of mitochondrial membrane potential with up-regulated pro-apoptotic Bax expression, down-regulated anti-apoptotic Bcl-2 expression and cytochrome c release from mitochondria to cytosol. Collectively, the data suggest that 5-FU is effective in inducing cell growth reduction and apoptosis, in part, by reducing phosphorylation of pRB and activating mitochondrial dysfunction in CHP-100 cells.

Modeling for the fate of Organic Chemicals in a Multi-media Environment Using MUSEM (다매체 환경 모델 MUSEM을 이용한 유해화학물질의 환경거동예측 모델링)

  • Roh, Kyong-Joon;Kim, Dong-Myung
    • Journal of the Korean Society for Marine Environment & Energy
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    • v.10 no.4
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    • pp.201-210
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    • 2007
  • Pollution by chemical substances such as POPs, EDCs and PBTs in the ecosystem has become more complex and varied, increasing the possibility of irreversible damage to human health or the ecosystem. It is necessary to have a exposure assessment in a multi-media environment for various chemical substances is required for efficient management. This study applied MUSEM(Multi-media Simplebox-systems Environmental Model), a multimedia environmental model that can simultaneously evaluate the possibility of exposure of hundreds of chemical substances in order to efficiently manage chemical substances that can have negative impact on human health or ecological environment through environmental contamination. MUSEM executed the modeling for Japan by setting all 47 prefectures of japan as the regional area for 62 chemical substances and the rest of the territory of japan, excluding regional area, as the continental area and made the estimation of concentration among environment media in each administrative area and made the sensitivity analysis on Tokyo area. The results of simulation for chemical distribution showed that most of the target chemicals located in water region. The result of sensitivity analysis for octanol-water partition rate showed that the concentration change of soil in urban/industrial area and sediment in freshwater was high. In the case of sensitivity analysis for degradation rate showed that the concentration change of freshwater, soil in urban/industrial area, and sediment in freshwater was high.

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