多氯联苯对人肺成纤维细胞的双相剂量效应研究
发布时间：2022-12-06 19:14
毒理学的核心内容是剂量效应关系,以进行风险评估与管理。剂量效应关系通常采用阈值模型（主要应用于非致癌物）和线性非阈值模型（主要应用于致癌物）。近年来,一种新的剂量效应关系模型即低剂量刺激、高剂量抑制的双相剂量效应（毒物兴奋效应）模型引起了广泛关注。双相剂量效应模型推翻了传统毒理学关于可通过毒物在高剂量下的效应外推其在低剂量时的效应的假设,因而对当前的风险评估工作是一种挑战。近几十年来,基于生物（如老鼠、细菌、微藻、细胞等）的生长、繁殖、寿命、生物发光等指标,建立的活体与离体生物实验模型被广泛用于毒理学研究,使得毒性测试快速、廉价、可重复、稳定、灵敏、可靠,因而已被应用于实际的毒性测试和生态风险评价。肺是高度血管化的器官,暴露于大量通过呼吸和血液循环进入的异生质化合物如多氧联苯（Polychlorinated biphenyls, PCBs）,因此,肺易受这些有毒化学品的侵害。本文以不同氯代数和不同结构的四种PCBs同系物为受试化合物,包括2,2’,3,3’-tetrachlorobiphenyl （PCB40,非共平面4氯）,3,3’,4,4’-tetrachlorobiphenyl ...
【文章页数】：109 页
【学位级别】：博士
【文章目录】：
Acknowledgements
Abstract
摘要
Table of Contents
List of Tables
List of Figures
Chapter 1 Introduction
1.1. Biphasic dose-response
1.2. Biphasic dose response and its universality
1.3. Significance of biphasic dose response in Environmental Science and risk assessmentpractices
1.4. Polychlorinated bipheuyls sources and transmission routes
1.5. PCBs exposure routes and health effects
1.6. Human lungs fibroblast cell
1.7. Progress in biphasic dose response using growth as end point
1.8. Molecular and cellular mechanisms of biphasic responses
1.8.1. Receptor-mediated and cell signaling-mediated biphasic mechanisms
1.8.2. Antagonist-mediated enhancement of inhibitory responses
1.9. PCB mediated biphasic dose response mechanisms using in-vivo model
1.10. PCB mediated biphasic dose response mechanisms using in-vitro model
1.11. Objectives of the study
1.12. Research Idea
Chapter 2 Structure dependent four chlorinated PCBs cytotoxic effects to HELF cells andpotential molecular mechanisms
2.1. Introduction
2.2. Materials and methods
2.2.1. Chemicals and reagents
2.2.2. Cell culture
2.2.3. Cell proliferation
2.2.4. Cell cycle distribution and membrane integrity determination
2.2.5. Western blot analysis
2.2.6. Statistical analysis
2.3. Results
2.3.1. HELF cells proliferation induced by PCB40 and PCB77
2.3.2. Response of membrane integrity
2.3.3. HELF cell cycle and apoptosis
2.3.4. Cyclin,kinases and capases protein expression
2.4. Discussion
2.5. Conclusion
Chapter 3 Biphasic dose response of non-coplanar and coplanar PCB with five chlorinationexposed to HELF cells and potential molecular mechanisms
3.1. Introduction
3.2. Materials and methods
3.2.1. Chemicals and reagents
3.2.2. Cell culture
3.2.3. Cell proliferation test
3.2.4. Measurement of oxidative stress
3.2.5. Measurement of antioxidant enzymes
3.2.6. Measuremnt of DNA damage
3.2.7. Protein assay
3.2.8. Western blot analysis
3.2.9. Statistical analysis
3.3. Results
3.3.1. HELF cells proliferation induced by PCB101 and PCB118
3.3.2. Oxidative stress induced by PCB101 and PCB118
3.3.3. Antioxidant enzymes induced by PCB101 and PCB118
3.3.4. DNA damage induced by PCB101 and PCB118
3.3.5. Response of MAPK proteins exposed to PCB101 and PCB118
3.4. Discussion
3.5. Conclusion
Chapter 4 Conclusion and future perspectives
4.1 Research a biphasic dose-response relationship by PCBs congeners
4.1.1 Cellular process and oxidative stress
4.1.2 Cell cycle related protein and MAPK pathway
4.2 Application of the research
4.3 Prospects
References
Curriculum Vitae
本文编号：3711482
【文章页数】：109 页
【学位级别】：博士
【文章目录】：
Acknowledgements
Abstract
摘要
Table of Contents
List of Tables
List of Figures
Chapter 1 Introduction
1.1. Biphasic dose-response
1.2. Biphasic dose response and its universality
1.3. Significance of biphasic dose response in Environmental Science and risk assessmentpractices
1.4. Polychlorinated bipheuyls sources and transmission routes
1.5. PCBs exposure routes and health effects
1.6. Human lungs fibroblast cell
1.7. Progress in biphasic dose response using growth as end point
1.8. Molecular and cellular mechanisms of biphasic responses
1.8.1. Receptor-mediated and cell signaling-mediated biphasic mechanisms
1.8.2. Antagonist-mediated enhancement of inhibitory responses
1.9. PCB mediated biphasic dose response mechanisms using in-vivo model
1.10. PCB mediated biphasic dose response mechanisms using in-vitro model
1.11. Objectives of the study
1.12. Research Idea
Chapter 2 Structure dependent four chlorinated PCBs cytotoxic effects to HELF cells andpotential molecular mechanisms
2.1. Introduction
2.2. Materials and methods
2.2.1. Chemicals and reagents
2.2.2. Cell culture
2.2.3. Cell proliferation
2.2.4. Cell cycle distribution and membrane integrity determination
2.2.5. Western blot analysis
2.2.6. Statistical analysis
2.3. Results
2.3.1. HELF cells proliferation induced by PCB40 and PCB77
2.3.2. Response of membrane integrity
2.3.3. HELF cell cycle and apoptosis
2.3.4. Cyclin,kinases and capases protein expression
2.4. Discussion
2.5. Conclusion
Chapter 3 Biphasic dose response of non-coplanar and coplanar PCB with five chlorinationexposed to HELF cells and potential molecular mechanisms
3.1. Introduction
3.2. Materials and methods
3.2.1. Chemicals and reagents
3.2.2. Cell culture
3.2.3. Cell proliferation test
3.2.4. Measurement of oxidative stress
3.2.5. Measurement of antioxidant enzymes
3.2.6. Measuremnt of DNA damage
3.2.7. Protein assay
3.2.8. Western blot analysis
3.2.9. Statistical analysis
3.3. Results
3.3.1. HELF cells proliferation induced by PCB101 and PCB118
3.3.2. Oxidative stress induced by PCB101 and PCB118
3.3.3. Antioxidant enzymes induced by PCB101 and PCB118
3.3.4. DNA damage induced by PCB101 and PCB118
3.3.5. Response of MAPK proteins exposed to PCB101 and PCB118
3.4. Discussion
3.5. Conclusion
Chapter 4 Conclusion and future perspectives
4.1 Research a biphasic dose-response relationship by PCBs congeners
4.1.1 Cellular process and oxidative stress
4.1.2 Cell cycle related protein and MAPK pathway
4.2 Application of the research
4.3 Prospects
References
Curriculum Vitae
本文编号：3711482
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