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WORTMANNIN Affect Cellular Response by Radiation |
LI Yu, LI Bai-long |
Radiation Department in Navy Medical Faculty, Second Military Medical University, Shanghai 200433 China |
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Abstract Objective To observe radiation Response of cells by WORTMANNIN (WT),which is inhibitor for Phosphatidylinositol-3 Kinase (PI-3K).Methods LP3 cells are prepared with different concentration of WT for 1 hour and receive different dose γ irradiation.To continue the cell for clone culture,and get the production of dose-survival curve.1800 pulsed-field gel electrophoresis is used to detect DNA double-strand breaks after the 20Gyγirradiation.Continue to use the mobility shift assays (Electrophoresis Mobility Shift Assay,EMSA)to observe NF-kB transcription factor of the corresponding changes.Result WT can be found to increase the radiation sensitivity of SP3 cells,the best sensitizer concentration in 20μmol/L or more,obvious sensitizing effect within 6h time;the electrophoresis experiments showed that after irradiation with time,by 50μmol/L WT group DNA the gel is higher than that of the simple exposure group;transcription factor NF-kB binding activity in the 6 hours after exposure experiences a low-rise and then the process of rising with its the peak of the change reaching after about 3 hours after irradiation.Conclusion It suggests the existence of PI-3K-mediated radiation sensitizer pathways.Ionizing radiation may activate NF-kB,which caused some DNA damage repair and other defense mechanisms and cell-related gene activity in order to reduce radiation damage.WT may block this process through the early stages of radiation-sensitizing effect.
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Received: 23 June 2009
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