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The Mechanism Of The Low Dose Radiation Biological Effect

Posted on:2010-02-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y XuFull Text:PDF
GTID:1114360272496776Subject:Internal Medicine
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The difference between low dose radiation and high dose radiation has been proven by many experiments. High dose radiation is harmful for humanbeing.However; low dose radiation can produce the adaptive effect and improve the immunity. The mechanism of the low dose radiation has not been clear. DNA repair may be related to the adaptive effect.P53 play an important role in the adaptive effect. The protein synthesis and metabolism all take part in the low dose radiation effect.Hepatocellular carcinoma is frequent occurrence in our country. The main treatment is operation. But limited to the local site of tumor and adjuvant vessels, operation is limited. At the same time, the carcinoma is not sensitive to the chemotherapy. The radiotherapy has played a role in the treatment. But the tumor cell radiation dose is larger than the normal cell endurance dose. So the radiotherapy is limited. How to improve the radiotherapy effect and reduce the harm effect is questional.The low dose combined with the high dose radiation can increase the apoptosis of tumor cell.The research is mainly focus on the BEL7402 cell line and HL7702 cell line effect after low dose radiation. Further explore the mechanism of the different effect; mainly included the PDK1 and the following protein, such as p27, Akt and Rb.Our project can make some theory base to the focus site of radiotherapy.Part 1 the different effect of normal cell and tumor cell and the mechism1. The effect on proliferation and cell cycle of LDR on normal cell and tumor cell25 mGy,50 mGy,75 mGy,100 mGy,200 mGy low dose radiation and 1 Gy high dose radiation on HL7702,6550HLEpiC,293T and BEL7402,HCT-8 and Hela cell line. After radiation, different time cell count, MTT experiment and flowcytometry to explore the cell cycle. The results showed that the low dose radiation can stimulate the proliferation of normal cell line. But the tumor cell proliferation was not changed. The LDR had no effect on the cell cycle of normal cell and tumor cell line.2. The mechanism of LDR on tumor cell and normal cellIn order to explore the different effect mechanism, we used the protein array to find protein changes related to cell cycle. Many protein expressions has been changed after LDR.Our experiment has found that phospharylated Rb protein expression has been increase after LDR in human bone marrow mechymal stem cell. The Rb protein play an important role in G1 to S swith.The phospharylated Rb protein free the E2F factor and take part in cell cycle regulation. Our experiment observed that the phosphorylated Rb protein decreased in BEL7402 and increased in HL7702 cell line.2.1 The phospharylated Rb protein expression in HL7702 cell line and BEL7402 cell line. The phospharylated Rb protein expression was increased in HL7702 cell line after LDR.In BEL7402 cell line the phospharylated Rb protein expression decreased after LDR.2.2 The cyclinD1 expression in HL7702 cell line and BEL7402 cell line The expression of cyclinD1 increased in HL7702 cell line after LDR, and decreased in BEL7402 cell line after LDR.2.3 The expression of phospharylated PDK1 in HL7702 cell line and BEL7402 cell line. The phospharylaed PDK1 expression increased in HL7702 cell line after LDR, and decreased in BEL7402 cell line after LDR.2.4 The expression of phospharylate Akt in HL7702 and BEL7402 cell line. The expression of phospharylaed of Akt expression increased in HL7702 cell line and decreased in BEL7402 cell line after LDR. Part2 the adaptive effect of LDR and mechanism1. The effect on normal cell and tumor cell proliferation of LDR combined with high dose radiationHL7702 cell line and BEL7402 cell line were irradiated by low dose radiation and combined with high dose radiation. The cell count and flowcytometry carried on after the radiation. There was adaptive effect on HL7702 cell line but no adaptive in EBL7402 cell line. The apoptosis increased in BEL7402 cell line after low dose radiation combined with high dose radiation.2. The mechanism of LDR combined with high dose radiation in HL7702 and BEL7402 cell line.The protein related to cell cycle has been explored by protein array. Some protein expression increased and some decreased.PI3K/Akt cell signaling pathway mainly regulate the cell apoptosis, proliferation and differentiation. So we explore the expression of Akt and related protein expression.2.1 The expression of p27 in HL7702 and BEL7402 cell line after LDR combined with high dose radiation. The expression of p27 increased in HL7702 and BEL7402 cell line. The expression was more in the combined group in BEL7402 cell line. But less in the combined group in HL7702 cell line.2.2 The expression of phospharylated Rb in HL7702 cell line and BEL7402 cell line after LDR combined with high dose radiationThe expression of p-Rb decreased in HL7702 and BEL7402 cell line. The expression was less in the combined group in BEL7402 cell line. But more in the combined group in HL7702 cell line.2.3 The expression of phospharylated Akt in HL7702 cell line and BEL7402 cell line after LDR combined with high dose radiationThe expression of p-Akt increased in HL7702 and BEL7402 cell line. The expression was less in the combined group in HL7702 cell line. But more in the combined group in BEL7402 cell line.2.4 The expression of phospharylated PDK1 in HL7702 cell line and BEL7402 cell line after LDR combined with high dose radiationThe expression of p-PDK1 decreased in HL7702 and BEL7402 cell line. The expression was less in the combined group in BEL7402 cell line. But more in the combined group in HL7702 cell line.2.5 The expression of cyclinD1 in HL7702 cell line and BEL7402 cell line after LDR combined with high dose radiationThe expression of p-PDK1 decreased in HL7702 and BEL7402 cell line. The expression was less in the combined group in BEL7402 cell line. But more in the combined group in HL7702 cell line.In one word, LDR can produce the stimulating and adaptive effect on normal cell but not in tumor cell. The protein of PDK1, Rb may be related to the effect.
Keywords/Search Tags:Radiation, cell, signaling transduction, PDK1, Rb
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