| Acknowledgements | 第10-12页 |
| Abstract | 第12-14页 |
| 摘要 | 第15-18页 |
| Table of Contents | 第18-21页 |
| List of Tables | 第21-22页 |
| List of Figures | 第22-26页 |
| Chapter 1 Introduction | 第26-44页 |
| 1.1. Biphasic dose-response | 第26-27页 |
| 1.2. Biphasic dose response and its universality | 第27-28页 |
| 1.3. Significance of biphasic dose response in Environmental Science and risk assessmentpractices | 第28-30页 |
| 1.4. Polychlorinated bipheuyls sources and transmission routes | 第30页 |
| 1.5. PCBs exposure routes and health effects | 第30-32页 |
| 1.6. Human lungs fibroblast cell | 第32-33页 |
| 1.7. Progress in biphasic dose response using growth as end point | 第33-34页 |
| 1.8. Molecular and cellular mechanisms of biphasic responses | 第34-37页 |
| 1.8.1. Receptor-mediated and cell signaling-mediated biphasic mechanisms | 第35-36页 |
| 1.8.2. Antagonist-mediated enhancement of inhibitory responses | 第36-37页 |
| 1.9. PCB mediated biphasic dose response mechanisms using in-vivo model | 第37页 |
| 1.10. PCB mediated biphasic dose response mechanisms using in-vitro model | 第37-42页 |
| 1.11. Objectives of the study | 第42-43页 |
| 1.12. Research Idea | 第43-44页 |
| Chapter 2 Structure dependent four chlorinated PCBs cytotoxic effects to HELF cells andpotential molecular mechanisms | 第44-60页 |
| 2.1. Introduction | 第44-46页 |
| 2.2. Materials and methods | 第46-49页 |
| 2.2.1. Chemicals and reagents | 第46-47页 |
| 2.2.2. Cell culture | 第47页 |
| 2.2.3. Cell proliferation | 第47页 |
| 2.2.4. Cell cycle distribution and membrane integrity determination | 第47-48页 |
| 2.2.5. Western blot analysis | 第48页 |
| 2.2.6. Statistical analysis | 第48-49页 |
| 2.3. Results | 第49-57页 |
| 2.3.1. HELF cells proliferation induced by PCB40 and PCB77 | 第49-51页 |
| 2.3.2. Response of membrane integrity | 第51页 |
| 2.3.3. HELF cell cycle and apoptosis | 第51-56页 |
| 2.3.4. Cyclin,kinases and capases protein expression | 第56-57页 |
| 2.4. Discussion | 第57-59页 |
| 2.5. Conclusion | 第59-60页 |
| Chapter 3 Biphasic dose response of non-coplanar and coplanar PCB with five chlorinationexposed to HELF cells and potential molecular mechanisms | 第60-83页 |
| 3.1. Introduction | 第60-63页 |
| 3.2. Materials and methods | 第63-67页 |
| 3.2.1. Chemicals and reagents | 第63页 |
| 3.2.2. Cell culture | 第63页 |
| 3.2.3. Cell proliferation test | 第63-64页 |
| 3.2.4. Measurement of oxidative stress | 第64页 |
| 3.2.5. Measurement of antioxidant enzymes | 第64-65页 |
| 3.2.6. Measuremnt of DNA damage | 第65-66页 |
| 3.2.7. Protein assay | 第66页 |
| 3.2.8. Western blot analysis | 第66页 |
| 3.2.9. Statistical analysis | 第66-67页 |
| 3.3. Results | 第67-77页 |
| 3.3.1. HELF cells proliferation induced by PCB101 and PCB118 | 第67-69页 |
| 3.3.2. Oxidative stress induced by PCB101 and PCB118 | 第69-71页 |
| 3.3.3. Antioxidant enzymes induced by PCB101 and PCB118 | 第71-73页 |
| 3.3.4. DNA damage induced by PCB101 and PCB118 | 第73-75页 |
| 3.3.5. Response of MAPK proteins exposed to PCB101 and PCB118 | 第75-77页 |
| 3.4. Discussion | 第77-81页 |
| 3.5. Conclusion | 第81-83页 |
| Chapter 4 Conclusion and future perspectives | 第83-86页 |
| 4.1 Research a biphasic dose-response relationship by PCBs congeners | 第83-84页 |
| 4.1.1 Cellular process and oxidative stress | 第84页 |
| 4.1.2 Cell cycle related protein and MAPK pathway | 第84页 |
| 4.2 Application of the research | 第84-85页 |
| 4.3 Prospects | 第85-86页 |
| References | 第86-103页 |
| Curriculum Vitae | 第103-109页 |
