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A Study Of Effects Of Ionizing Radiation And Radiosensitivity Regulating On Key Target Cells In Radiation-induced Pulmonary Injury

Posted on:2007-12-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y H TanFull Text:PDF
GTID:1104360185970440Subject:Respiratory medicine
Abstract/Summary:PDF Full Text Request
The radiation-induced pulmonary injury is one of the most important dose-limiting toxicity for radiation therapy of tumours in the thoracic region. The pulmonary parenchyma cell damage have been demonstrated to initiate interstitial inflammatory and the remodeling of lung tissue. Therefore, more studies on the effect of ionizing radiation on pulmonary parenchyma cell, and on the change of cellular proliferation and appoptosis and function, and deeper isights into the manipulation of the radiosensitivity of pulmonary parenchyma cells are focus on the defense research of radiation-induced pulmonary injury.Ionizing radiation produces cells lesions largely through the generation of ractive oxygen species (ROS) that attack DNA. The DNA base excision repair pathyway is responsible for the repair of oxidative DNA damage. A crucial step in the base excision repair pathway involves the cleavage of an apurinic/apyrimidinic (AP) site in DNA by an AP endonuclease (APE). Ape1 as the major AP endonuclease in mammalian cell is a critical component of the base excision pathway. The increased levels of Ape1 protein are associated noticeably with the radioresistance in many kinds of human tumours. A recent study have demonstrated that tumours became more sensitivity to chemo- and radiation when APE1 levels in tumour cells was decreased using silencing RNA (siRNA) targeting technology in the osteosarcoma cell line, human osteogenic sarcoma (HOS). So, it is likely that the DNA repair enzyme human Ape1 is a potential molecular target to manipulate cells intrinsic radiosensitivity.At present, however, it is unclear about the mechanism of radiation-induced pulmonary injury, and a little information is available about the biologic effect of ionizing radiaton on pulmonary parenchyma cells. How to inspect the effect of ionizing radiation on pulmonary parenchyma cells all round? How to evaluate the intrinsic radiosensitivity of cells simply and quickly? Can we control the rasiosensitivity of cells by regulating the levels of Ape1 protein? Answers to these problems above are useful to explain the role of the key taget cells in radiation-induced pulmonary injury and clarify the mechanism of the...
Keywords/Search Tags:pulmonary injury/radiation-induced, endothelial cell, DNA damage, TGF-β1, apurinic/apyrimidinic endonuclease(Ape1), radiosensitivity
PDF Full Text Request
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