請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81641完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 劉貞佑(Chen-Yu Liu) | |
| dc.contributor.author | Chun-Chieh Hung | en |
| dc.contributor.author | 洪浚傑 | zh_TW |
| dc.date.accessioned | 2022-11-24T09:25:05Z | - |
| dc.date.available | 2022-11-24T09:25:05Z | - |
| dc.date.copyright | 2021-08-30 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-07-29 | |
| dc.identifier.citation | 1. Moody, C.A. and J.A. Field, Perfluorinated surfactants and the environmental implications of their use in fire-fighting foams. Environmental science technology, 2000. 34(18): p. 3864-3870. 2. Susmann, H.P., et al., Dietary habits related to food packaging and population exposure to PFASs. Environmental health perspectives, 2019. 127(10): p. 107003. 3. Sharma, B.M., et al., Perfluoroalkyl substances (PFAS) in river and ground/drinking water of the Ganges River basin: emissions and implications for human exposure. Environmental pollution, 2016. 208: p. 704-713. 4. Domingo, J.L. and M. Nadal, Per-and polyfluoroalkyl substances (PFASs) in food and human dietary intake: a review of the recent scientific literature. Journal of agricultural and food chemistry, 2017. 65(3): p. 533-543. 5. Olsen, G.W., et al., Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environmental health perspectives, 2007. 115(9): p. 1298-1305. 6. Ngo, H.T., et al., In utero exposure to perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) did not increase body weight or intestinal tumorigenesis in multiple intestinal neoplasia (Min/+) mice. Environmental research, 2014. 132: p. 251-263. 7. Olsen, G.W., et al., Epidemiologic assessment of worker serum perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) concentrations and medical surveillance examinations. Journal of occupational and environmental medicine, 2003. 45(3): p. 260-270. 8. Trudel, D., et al., Estimating consumer exposure to PFOS and PFOA. Risk Analysis: An International Journal, 2008. 28(2): p. 251-269. 9. Chen, W.-L., et al., Concentrations of perfluoroalkyl substances in foods and the dietary exposure among Taiwan general population and pregnant women. Journal of food and drug analysis, 2018. 26(3): p. 994-1004. 10. Stahl, T., D. Mattern, and H. Brunn, Toxicology of perfluorinated compounds. Environmental Sciences Europe, 2011. 23(1): p. 1-52. 11. Gallo, V., et al., Serum perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) concentrations and liver function biomarkers in a population with elevated PFOA exposure. Environmental health perspectives, 2012. 120(5): p. 655-660. 12. Kataria, A., et al., Association between perfluoroalkyl acids and kidney function in a cross-sectional study of adolescents. Environmental health, 2015. 14(1): p. 89. 13. Qin, X.-D., et al., Association of perfluoroalkyl substances exposure with impaired lung function in children. Environmental research, 2017. 155: p. 15-21. 14. Vuong, A.M., et al., Prenatal polybrominated diphenyl ether and perfluoroalkyl substance exposures and executive function in school-age children. Environmental research, 2016. 147: p. 556-564. 15. Maisonet, M., et al., Maternal concentrations of polyfluoroalkyl compounds during pregnancy and fetal and postnatal growth in British girls. Environmental health perspectives, 2012. 120(10): p. 1432-1437. 16. Thomas, J., et al., Comparative analyses of multi-species sequences from targeted genomic regions. Nature, 2003. 424(6950): p. 788-793. 17. Wan, H., et al., PFOS-induced hepatic steatosis, the mechanistic actions on β-oxidation and lipid transport. Biochimica et Biophysica Acta (BBA)-General Subjects, 2012. 1820(7): p. 1092-1101. 18. Xia, W., et al., PFOS prenatal exposure induce mitochondrial injury and gene expression change in hearts of weaned SD rats. Toxicology, 2011. 282(1-2): p. 23-29. 19. Chou, H.-C., et al., From the cover: l-carnitine via PPARγ-and Sirt1-dependent mechanisms attenuates epithelial-mesenchymal transition and renal fibrosis caused by perfluorooctanesulfonate. Toxicological Sciences, 2017. 160(2): p. 217-229. 20. López-Doval, S., et al., Perfluorooctane sulfonate effects on the reproductive axis in adult male rats. Environmental research, 2014. 134: p. 158-168. 21. Mao, Z., et al., Perfluorooctane sulfonate induces apoptosis in lung cancer A549 cells through reactive oxygen species‐mediated mitochondrion‐dependent pathway. Journal of Applied Toxicology, 2013. 33(11): p. 1268-1276. 22. Ye, L., et al., Gene expression profiling in fetal rat lung during gestational perfluorooctane sulfonate exposure. Toxicology letters, 2012. 209(3): p. 270-276. 23. Berger, J. and D.E. Moller, The mechanisms of action of PPARs. Annual review of medicine, 2002. 53(1): p. 409-435. 24. Bjork, J., J. Butenhoff, and K.B. Wallace, Multiplicity of nuclear receptor activation by PFOA and PFOS in primary human and rodent hepatocytes. Toxicology, 2011. 288(1-3): p. 8-17. 25. Desvergne, B. and W. Wahli, Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocrine reviews, 1999. 20(5): p. 649-688. 26. Hashimoto, T., et al., Defect in peroxisome proliferator-activated receptor α-inducible fatty acid oxidation determines the severity of hepatic steatosis in response to fasting. Journal of Biological Chemistry, 2000. 275(37): p. 28918-28928. 27. Vanden Heuvel, J.P., et al., Differential activation of nuclear receptors by perfluorinated fatty acid analogs and natural fatty acids: a comparison of human, mouse, and rat peroxisome proliferator-activated receptor-α,-β, and-γ, liver X receptor-β, and retinoid X receptor-α. Toxicological Sciences, 2006. 92(2): p. 476-489. 28. Yu, Y., et al., A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages. Nature Communications, 2014. 5. 29. Braissant, O., et al., Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha,-beta, and-gamma in the adult rat. Endocrinology, 1996. 137(1): p. 354-366. 30. Yu, Y., et al., A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages. Nature communications, 2014. 5(1): p. 1-11. 31. Moore, L.D., T. Le, and G. Fan, DNA methylation and its basic function. Neuropsychopharmacology, 2013. 38(1): p. 23-38. 32. Bird, A., Perceptions of epigenetics. Nature, 2007. 447(7143): p. 396. 33. Wan, Y.-j., et al., Alterations in tumor biomarker GSTP gene methylation patterns induced by prenatal exposure to PFOS. Toxicology, 2010. 274(1-3): p. 57-64. 34. Guo, X.-X., et al., Brain-derived neurotrophic factor mediated perfluorooctane sulfonate induced-neurotoxicity via epigenetics regulation in SK-N-SH cells. International journal of molecular sciences, 2017. 18(4): p. 893. 35. Wen, Y., et al., Effect of PFOA on DNA methylation and alternative splicing in mouse liver. Toxicology letters, 2020. 329: p. 38-46. 36. Tian, J., et al., SAM targeting methylation by the methyl donor, a novel therapeutic strategy for antagonize PFOS transgenerational fertilitty toxicity. Ecotoxicology and environmental safety, 2019. 184: p. 109579. 37. Razin, A. and H. Cedar, DNA methylation and gene expression. Microbiological reviews, 1991. 55(3): p. 451-458. 38. Olsen, G.W., et al., Temporal trends of perfluoroalkyl concentrations in American Red Cross adult blood donors, 2000–2010. Environmental science technology, 2012. 46(11): p. 6330-6338. 39. Klaunig, J.E., et al., Evaluation of the chronic toxicity and carcinogenicity of perfluorohexanoic acid (PFHxA) in Sprague-Dawley rats. Toxicologic pathology, 2015. 43(2): p. 209-220. 40. Bjork, J.A. and K.B. Wallace, Structure-activity relationships and human relevance for perfluoroalkyl acid–induced transcriptional activation of peroxisome proliferation in liver cell cultures. Toxicological Sciences, 2009. 111(1): p. 89-99. 41. Svingen, T., et al., Selection of reference genes for quantitative RT-PCR (RT-qPCR) analysis of rat tissues under physiological and toxicological conditions. PeerJ, 2015. 3: p. e855. 42. Sanders, J.M., et al., Disruption of estrogen homeostasis as a mechanism for uterine toxicity in Wistar Han rats treated with tetrabromobisphenol A. Toxicology and applied pharmacology, 2016. 298: p. 31-39. 43. Tuomi, J.M., et al., Bias in the Cq value observed with hydrolysis probe based quantitative PCR can be corrected with the estimated PCR efficiency value. Methods, 2010. 50(4): p. 313-322. 44. Zeybel, M., et al., Multigenerational epigenetic adaptation of the hepatic wound-healing response. Nature medicine, 2012. 18(9): p. 1369-1377. 45. Madi, T., et al., The determination of tissue‐specific DNA methylation patterns in forensic biofluids using bisulfite modification and pyrosequencing. Electrophoresis, 2012. 33(12): p. 1736-1745. 46. Qazi, M.R., et al., 28-Day dietary exposure of mice to a low total dose (7 mg/kg) of perfluorooctanesulfonate (PFOS) alters neither the cellular compositions of the thymus and spleen nor humoral immune responses: Does the route of administration play a pivotal role in PFOS-induced immunotoxicity? Toxicology, 2010. 267(1-3): p. 132-139. 47. Lau, C., et al., Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicological sciences, 2007. 99(2): p. 366-394. 48. Harrington, W.W., et al., The effect of PPARα, PPARδ, PPARγ, and PPARpan agonists on body weight, body mass, and serum lipid profiles in diet-induced obese AKR/J mice. PPAR research, 2007. 2007. 49. Lehrke, M., et al., Gaining weight: the Keystone Symposium on PPAR and LXR. Genes development, 2005. 19(15): p. 1737-1742. 50. Wolf, C.J., et al., Activation of mouse and human peroxisome proliferator− activated receptor alpha by perfluoroalkyl acids of different functional groups and chain lengths. Toxicological Sciences, 2008. 106(1): p. 162-171. 51. Shipley, J.M., et al., Trans-activation of PPARα and induction of PPARα target genes by perfluorooctane-based chemicals. Toxicological sciences, 2004. 80(1): p. 151-160. 52. Gibson, S. and J. Johnson, Absorption of FC-143-14C in rats after a single oral dose. Riker Laboratories, Inc., Subsidiary of M, 1979. 3. 53. Kataria, A., et al., Association between perfluoroalkyl acids and kidney function in a cross-sectional study of adolescents. Environmental Health, 2015. 14(1): p. 1-13. 54. Saikat, S., et al., The impact of PFOS on health in the general population: a review. Environmental Science: Processes Impacts, 2013. 15(2): p. 329-335. 55. Steenland, K., et al., Association of perfluorooctanoic acid and perfluorooctane sulfonate with serum lipids among adults living near a chemical plant. American journal of epidemiology, 2009. 170(10): p. 1268-1278. 56. Loveless, S.E., et al., Comparative responses of rats and mice exposed to linear/branched, linear, or branched ammonium perfluorooctanoate (APFO). Toxicology, 2006. 220(2-3): p. 203-217. 57. Austin, M.E., et al., Neuroendocrine effects of perfluorooctane sulfonate in rats. Environmental health perspectives, 2003. 111(12): p. 1485-1489. 58. Seacat, A.M., et al., Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats. Toxicology, 2003. 183(1-3): p. 117-131. 59. Qu, J.-H., et al., Perfluorooctane sulfonate-induced testicular toxicity and differential testicular expression of estrogen receptor in male mice. Environmental toxicology and pharmacology, 2016. 45: p. 150-157. 60. Rosen, M.B., et al., Toxicogenomic dissection of the perfluorooctanoic acid transcript profile in mouse liver: evidence for the involvement of nuclear receptors PPARα and CAR. Toxicological Sciences, 2008. 103(1): p. 46-56. 61. Tang, L.-L., et al., Mitochondrial toxicity of perfluorooctane sulfonate in mouse embryonic stem cell-derived cardiomyocytes. Toxicology, 2017. 382: p. 108-116. 62. Cheng, W., et al., Perfluorooctane sulfonate (PFOS) induced embryotoxicity and disruption of cardiogenesis. Toxicology in Vitro, 2013. 27(5): p. 1503-1512. 63. Zeng, H.c., et al., Prenatal exposure to PFOS caused mitochondia‐mediated apoptosis in heart of weaned rat. Environmental toxicology, 2015. 30(9): p. 1082-1090. 64. Wen, L.-L., et al., Perfluorooctanesulfonate mediates renal tubular cell apoptosis through PPARgamma inactivation. PloS one, 2016. 11(5): p. e0155190. 65. Du, Y., et al., Chronic effects of water-borne PFOS exposure on growth, survival and hepatotoxicity in zebrafish: a partial life-cycle test. Chemosphere, 2009. 74(5): p. 723-729. 66. Huang, Q., et al., Proteomic analysis of perfluorooctane sulfonate‐induced apoptosis in human hepatic cells using the iTRAQ technique. Journal of Applied Toxicology, 2014. 34(12): p. 1342-1351. 67. Sant, K.E., et al., Embryonic exposures to perfluorooctanesulfonic acid (PFOS) disrupt pancreatic organogenesis in the zebrafish, Danio rerio. Environmental pollution, 2017. 220: p. 807-817. 68. El‐Osta, A., DNMT cooperativity—the developing links between methylation, chromatin structure and cancer. Bioessays, 2003. 25(11): p. 1071-1084. 69. Sant, K.E., et al., Assessment of toxicological perturbations and variants of pancreatic islet development in the zebrafish model. Toxics, 2016. 4(3): p. 20. 70. Liu, S., N. Yin, and F. Faiola, PFOA and PFOS disrupt the generation of human pancreatic progenitor cells. Environmental Science Technology Letters, 2018. 5(5): p. 237-242. 71. Vandenberg, L.N., et al., Should oral gavage be abandoned in toxicity testing of endocrine disruptors? Environmental Health, 2014. 13(1): p. 1-7. 72. Sengupta, P., The laboratory rat: relating its age with human's. International journal of preventive medicine, 2013. 4(6): p. 624. 73. OECD, Test No. 407: Repeated Dose 28-day Oral Toxicity Study in Rodents. 2008. 74. Kim, H.-S., et al., Induction of apoptosis and CYP4A1 expression in Sprague-Dawley rats exposed to low doses of perfluorooctane sulfonate. The Journal of toxicological sciences, 2011. 36(2): p. 201-210. 75. Cui, L., et al., Studies on the toxicological effects of PFOA and PFOS on rats using histological observation and chemical analysis. Archives of environmental contamination and toxicology, 2009. 56(2): p. 338-349. 76. Nair, A.B. and S. Jacob, A simple practice guide for dose conversion between animals and human. Journal of basic and clinical pharmacy, 2016. 7(2): p. 27. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81641 | - |
| dc.description.abstract | 背景 全氟辛烷磺酸(PFOS)為八碳鏈結構的化學物質，由於其結構特性，因此其具有防水、防油的效果。常運用於表面處理、半導體製程中的光微影術部分、金屬去污溶劑以及食品器具表面塗層等，主要暴露途徑為透過受污染的食物和飲用水、使用相關產品及生產相關產品的職業暴露。且由於屬於持久性有機汙染物，在環境中及進入到體內皆不易被分解及排出。目前發現對於人體及動物都有負面效應的發生。 過氧化物酶體增殖物活化受體(PPAR)為核受體超家族的一員。在細胞生長、發育、分化與新陳代謝均有重要作用。核受體與配體結合後才會被活化並負責引導轉錄，由於核受體都位於細胞內部，因此它們的配體為脂溶性，這樣才能穿越由脂肪構成的細胞膜。PFOS由於其結構類似於脂肪酸，且對於核受體的親和力更高，因此容易引發相關作用。 DNA甲基化現象可調控轉錄，進而影響基因表達。於胚胎發展、出生後發育、癌症或環境荷爾蒙之影響等領域都是熱門的研究標的。當DNA進行甲基化修飾時，會抑制啟動子及轉錄起始點的轉錄作用，使基因表達量下降或不表達。 研究目的 本研究之目的為觀察暴露PFOS與各個器官Ppara和Pparg表現量的關聯性，並以DNA甲基化作為機制探討。 方法 五週齡大的Sprague Dawley雄性大鼠隨機分派到三個濃度點，包括0、5、10 mg/kg·d PFOS，每組6隻，暴露3週後犧牲取得血液、心臟、肝臟、肺臟、腎臟、胰臟及睪丸。基因表現量由定量即時聚合酶連鎖反應來進行測定；DNA甲基化則透過焦磷酸測序來進行。收集到的資料會以簡單線性回歸來觀察暴露PFOS、基因表現量及DNA甲基化的關聯性。 結果 在基因表現量的部分，暴露PFOS與血液的Ppara基因表現量(由Hprt校正：β = 2.00，p = 0.01；由Sdha校正：β= 0.20，p = 0.05)和腎臟的 Pparg 基因表現量(由Sdha校正：β = 1.49，p = 0.03)呈現正相關，而胰臟的Ppara基因表現量(由Sdha校正：β = -0.10，p < 0.01)則呈現負相關。 在DNA甲基化的部分，暴露PFOS與Ppara在心臟(位點2：β = 0.09，p = 0.05)與胰臟(位點3：β = 0.09; p = 0.02)的甲基化程度呈現正相關；Pparg則是在胰臟(位點3：β = 0.22，p = 0.02) 與肺臟(位點6：β = 0.51，p < 0.01)的甲基化程度呈現正相關，而血液(位點4：β = -0.60，p = 0.03；位點5：β = -0.57，p = 0.05；位點6：β = -0.53，p = 0.04)則呈現負相關。 在DNA甲基化與基因表現量的關聯性中，我們發現Pparg在心臟(由Sdha校正；位點3：β = 0.61；95% confidence interval = 0.01 to 1.20；p = 0.05；位點5：β = 1.00；95% confidence interval = 0.40 to 1.60；p < 0.01)呈現正相關，而胰臟(由Sdha校正；位點1：β = -1.35，p = 0.05；位點5：β = -1.07，p = 0.05)則呈現負相關。 儘管沒有器官在三個路徑皆達到統計顯著，不過在胰臟Pparg可以觀察到暴露PFOS會影響到DNA甲基化，而影響到基因表現量，可推測DNA甲基化可能在這之中有一定的影響力。 結論 本研究指出，暴露PFOS對大鼠的Ppara和Pparg的DNA甲基化及基因表現量有影響，尤其是胰臟Pparg，後續研究可針對其他甲基化位點以及上下游基因表現量做更進一步的探討。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T09:25:05Z (GMT). No. of bitstreams: 1 U0001-2707202113584700.pdf: 4413139 bytes, checksum: 43039b6e7786ca2fbdfe44c2d089c39a (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 中文摘要 I Abstract III List of Figures IX List of Tables XI Chapter 1 Introduction 1 1.1 Perfluorooctane Sulfonate (PFOS) 1 1.2 Peroxisome Proliferator-Activated Receptors (PPARs) 3 1.3 DNA methylation 5 1.4 Study Aims 6 Chapter 2 Materials and Methods 7 2.1 Laboratory Animals 7 2.2 RNA Extraction 8 2.2.1 Selection of homogenization conditions 8 2.2.2 RNA Extraction for tissues 8 2.2.3 RNA Extraction for blood 9 2.3 cDNA Synthesis 11 2.4 qPCR 13 2.4.1 Adjustments of experimental parameters 13 2.4.2 Selection of Reference Gene 13 2.4.3 qPCR Procedure 13 2.4.4 Parameters that Evaluate Standard Curves 15 2.5 DNA Extraction 16 2.6 Bisulfite Treatment 17 2.7 Bisulfite Converted DNA PCR 19 2.8 Capillary Electrophoresis 21 2.9 Pyrosequencing 21 2.10 Statistical Analysis 23 Chapter 3 Results 25 3.1 Descriptive Analysis for Physiological Value 25 3.2 Standard Curve for Reference Genes and Target Genes 26 3.3 Relative Ppara and Pparg Gene Expression to PFOS Exposure 26 3.4 Ppara and Pparg DNA Methylation Changes in Relation to PFOS Exposure 27 3.5 Association between DNA methylation and Relative Gene Expression in Ppara and Pparg 29 Chapter 4 Discussion 31 4.1 Results Compared to Human 31 4.2 The Relationship between PFOS Exposure and Physiological Value 32 4.3 The Relationship between PFOS Exposure and Relative Gene Expression 33 4.4 The Relationship between PFOS Exposure and DNA Methylation 36 4.5 The Relationship between DNA Methylation and Relative Gene Expression 37 4.6 Strengths and Limitations 39 Chapter 5 Conclusions 43 References 44 Figure 50 Table 59 Appendix 80 | |
| dc.language.iso | en | |
| dc.subject | DNA甲基化 | zh_TW |
| dc.subject | 全氟辛烷磺酸(PFOS) | zh_TW |
| dc.subject | Pparg | zh_TW |
| dc.subject | 相對基因表現量 | zh_TW |
| dc.subject | Ppara | zh_TW |
| dc.subject | PFOS | en |
| dc.subject | DNA methylation | en |
| dc.subject | Relative gene expression | en |
| dc.subject | Pparg | en |
| dc.subject | Ppara | en |
| dc.title | 全氟辛烷磺酸的暴露與大鼠PPAR基因表現量及DNA甲基化的關聯性 | zh_TW |
| dc.title | Perfluorooctane Sulfonate Exposure in Relation to PPARs’ Gene Expressions and DNA Methylation in a Rat Model | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 葉志清(Hsin-Tsai Liu),林靖愉(Chih-Yang Tseng),魏嘉徵,王如邦 | |
| dc.subject.keyword | 全氟辛烷磺酸(PFOS),Ppara,Pparg,相對基因表現量,DNA甲基化, | zh_TW |
| dc.subject.keyword | PFOS,Ppara,Pparg,Relative gene expression,DNA methylation, | en |
| dc.relation.page | 83 | |
| dc.identifier.doi | 10.6342/NTU202101797 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2021-07-29 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 食品安全與健康研究所 | zh_TW |
| 顯示於系所單位： | 食品安全與健康研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-2707202113584700.pdf 未授權公開取用 | 4.31 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。