Skip navigation

DSpace

機構典藏 DSpace 系統致力於保存各式數位資料(如:文字、圖片、PDF)並使其易於取用。

點此認識 DSpace
DSpace logo
English
中文
  • 瀏覽論文
    • 校院系所
    • 出版年
    • 作者
    • 標題
    • 關鍵字
    • 指導教授
  • 搜尋 TDR
  • 授權 Q&A
    • 我的頁面
    • 接受 E-mail 通知
    • 編輯個人資料
  1. NTU Theses and Dissertations Repository
  2. 公共衛生學院
  3. 職業醫學與工業衛生研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73464
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor楊孝友(Hsiao-Yu Yang)
dc.contributor.authorHsin-Yi Pengen
dc.contributor.author彭馨頤zh_TW
dc.date.accessioned2021-06-17T07:36:24Z-
dc.date.available2024-08-26
dc.date.copyright2019-08-26
dc.date.issued2019
dc.date.submitted2019-04-11
dc.identifier.citation1. Wade, W.A., et al., Severe Occupational Pneumoconiosis Among West Virginian Coal Miners One Hundred Thirty-eight Cases of Progressive Massive Fibrosis Compensated Between 2000 and 2009. Chest, 2011. 139(6): p. 1458-1462.
2. Cohen, R.A., Resurgent coal mine dust lung disease: wave of the future or a relic of the past? Occup Environ Med, 2016. 73(11): p. 715-716.
3. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans: Silica, Some Silicates, Coal Dust and Para-Aramid Fibrils. Lyon, 15-22 October 1996. IARC monographs on the evaluation of carcinogenic risks to humans, 1997. 68: p. 1-475.
4. Greenberg, M.I., J. Waksman, and J. Curtis, Silicosis: a review. Dis Mon, 2007. 53(8): p. 394-416.
5. Cox, C.W., C.S. Rose, and D.A. Lynch, State of the art: Imaging of occupational lung disease. Radiology, 2014. 270(3): p. 681-96.
6. Chen, P.C., et al., Diagnostic accuracy of breath tests for pneumoconiosis using an electronic nose. J Breath Res, 2017.
7. Shirasu, M. and K. Touhara, The scent of disease: volatile organic compounds of the human body related to disease and disorder. J Biochem, 2011. 150(3): p. 257-66.
8. Broza, Y.Y., et al., Hybrid volatolomics and disease detection. Angew Chem Int Ed Engl, 2015. 54(38): p. 11036-48.
9. Koek, M.M., et al., Quantitative metabolomics based on gas chromatography mass spectrometry: status and perspectives. Metabolomics, 2011. 7(3): p. 307-328.
10. Lubes, G. and M. Goodarzi, GC–MS based metabolomics used for the identification of cancer volatile organic compounds as biomarkers. Journal of Pharmaceutical and Biomedical Analysis, 2018. 147: p. 313-322.
11. van der Schee, M.P., et al., Breathomics in lung disease. Chest, 2015. 147(1): p. 224-231.
12. Filipiak, W., et al., Release of volatile organic compounds (VOCs) from the lung cancer cell line CALU-1 in vitro. Cancer Cell Int, 2008. 8: p. 17.
13. Chapman, E.A., P.S. Thomas, and D.H. Yates, Breath analysis in asbestos-related disorders: a review of the literature and potential future applications. J Breath Res, 2010. 4(3): p. 034001.
14. Buszewski, B., et al., Human exhaled air analytics: biomarkers of diseases. Biomedical Chromatography, 2007. 21(6): p. 553-566.
15. Calenic, B., et al., Oxidative stress and volatile organic compounds: interplay in pulmonary, cardio-vascular, digestive tract systems and cancer. Open Chemistry, 2015. 13(1): p. 1020-1030.
16. Phillips, M., et al., Effect of age on the breath methylated alkane contour, a display of apparent new markers of oxidative stress. J Lab Clin Med, 2000. 136(3): p. 243-9.
17. Yang, H.Y., et al., Development of breath test for pneumoconiosis: a case-control study. Respir Res, 2017. 18(1): p. 178.
18. Amann, A., et al., The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva. J Breath Res, 2014. 8(3): p. 034001.
19. Pleil, J., J. Beauchamp, and W. Miekisch, Cellular respiration, metabolomics and the search for illicit drug biomarkers in breath: report from PittCon 2017. J Breath Res, 2017. 11(3): p. 039001.
20. Zhang, A., et al., Cell metabolomics. OMICS, 2013. 17(10): p. 495-501.
21. Pleil, J.D., Breath biomarkers in toxicology. Arch Toxicol, 2016. 90(11): p. 2669-2682.
22. Stoppacher, N., et al., Identification and profiling of volatile metabolites of the biocontrol fungus Trichoderma atroviride by HS-SPME-GC-MS. Journal of Microbiological Methods, 2010. 81(2): p. 187-193.
23. Petavratzi, E., S. Kingman, and I. Lowndes, Particulates from mining operations: A review of sources, effects and regulations. Minerals Engineering, 2005. 18(12): p. 1183-1199.
24. Darquenne, C., Aerosol deposition in health and disease. Journal of aerosol medicine and pulmonary drug delivery, 2012. 25(3): p. 140-147.
25. Davies, C.N., Particle-fluid interaction. Journal of Aerosol Science, 1979. 10(5): p. 477-513.
26. Tanner, C.B. and M.L. Jackson, Nomographs of sedimentation times for soil particles under gravity or centrifugal acceleration. Soil Sci. Soc. Am. Proc., 1947. 12: p. 60-65.
27. Accessed March 4, 2019, A.a.-d.o.n.c.o.i.f.p.-s.e.m.m.I.-E.A.h.w.s.s.a.d.p.
28. Chiang, L.L., et al., Serum protein oxidation by diesel exhaust particles: effects on oxidative stress and inflammatory response in vitro. Chem Biol Interact, 2013. 206(2): p. 385-93.
29. Ritesh Kumar, S., et al., Cyto-genotoxicity of amphibole asbestos fibers in cultured human lung epithelial cell line: Role of surface iron. Toxicology and Industrial Health, 2010. 26(9): p. 575-582.
30. Lin, W., et al., In vitro toxicity of silica nanoparticles in human lung cancer cells. Toxicology and Applied Pharmacology, 2006. 217(3): p. 252-259.
31. Di Cesare, P.E., et al., Serum interleukin-6 as a marker of periprosthetic infection following total hip and knee arthroplasty. J Bone Joint Surg Am, 2005. 87(9): p. 1921-7.
32. ThermoFisher Scientific. Trypan Blue Exclusion. Available: https://www.thermofisher.com/tw/zt/home/references/gibco-cell-culture-basics/cell-culture-protocols/trypan-blue-exclusion.html Assessed March 16.
33. Jagannathan, L., S. Cuddapah, and M. Costa, Oxidative stress under ambient and physiological oxygen tension in tissue culture. Current pharmacology reports, 2016. 2(2): p. 64-72.
34. Kalluri, U., M. Naiker, and M.A. Myers, Cell culture metabolomics in the diagnosis of lung cancer-the influence of cell culture conditions. J Breath Res, 2014. 8(2): p. 027109.
35. Schallschmidt, K., et al., Investigation of cell culture volatilomes using solid phase micro extraction: Options and pitfalls exemplified with adenocarcinoma cell lines. Journal of Chromatography B, 2015. 1006(Supplement C): p. 158-166.
36. Agency, U.S.E.P., Compendium method TO-15: determination of volatile organic compounds (VOCs) in air collected in specially prepared canisters and analyzed by gas chromatography/mass spectrometry (GC/MS). 1999.
37. Smolinska, A., et al., Current breathomics--a review on data pre-processing techniques and machine learning in metabolomics breath analysis. J Breath Res, 2014. 8(2): p. 027105.
38. Pluskal, T., et al., MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinformatics, 2010. 11: p. 395.
39. Hayashi, S., et al., A novel application of metabolomics in vertebrate development. Biochem Biophys Res Commun, 2009. 386(1): p. 268-72.
40. Jiang, Y., et al., Identification and changes of different volatile compounds in meat of crucian carp under short-term starvation by GC-MS coupled with HS-SPME. Journal of Food Biochemistry, 2017. 41(3).
41. Niu, W., et al., Comparative evaluation of eight software programs for alignment of gas chromatography–mass spectrometry chromatograms in metabolomics experiments. Journal of Chromatography A, 2014. 1374: p. 199-206.
42. van den Berg, R.A., et al., Centering, scaling, and transformations: improving the biological information content of metabolomics data. BMC genomics, 2006. 7: p. 142-142.
43. Amal, H., et al., The scent fingerprint of hepatocarcinoma: in-vitro metastasis prediction with volatile organic compounds (VOCs). Int J Nanomedicine, 2012. 7: p. 4135-46.
44. Camino, G., S.M. Lomakin, and M. Lageard, Thermal polydimethylsiloxane degradation. Part 2. The degradation mechanisms. Polymer, 2002. 43(7): p. 2011-2015.
45. Kwak, J., et al., Volatile biomarkers from human melanoma cells. J Chromatogr B Analyt Technol Biomed Life Sci, 2013. 931: p. 90-6.
46. Thriumani, R., et al., A study on volatile organic compounds emitted by in-vitro lung cancer cultured cells using gas sensor array and SPME-GCMS. BMC Cancer, 2018. 18(1): p. 362.
47. Smith, D. and P. Spanel, On the importance of accurate quantification of individual volatile metabolites in exhaled breath. J Breath Res, 2017. 11(4): p. 047106.
48. Buszewski, B., et al., Human exhaled air analytics: biomarkers of diseases. Biomed Chromatogr, 2007. 21(6): p. 553-66.
49. Li, Y., J.H. Li, and H. Xu, Graphene/polyaniline electrodeposited needle trap device for the determination of volatile organic compounds in human exhaled breath vapor and A549 cell. Rsc Advances, 2017. 7(20): p. 11959-11968.
50. Chen, X., et al., A study of the volatile organic compounds exhaled by lung cancer cells in vitro for breath diagnosis. Cancer, 2007. 110(4): p. 835-44.
51. Sponring, A., et al., Release of volatile organic compounds from the lung cancer cell line NCI-H2087 in vitro. Anticancer Res, 2009. 29(1): p. 419-26.
52. Filipiak, W., et al., TD-GC-MS analysis of volatile metabolites of human lung cancer and normal cells in vitro. Cancer Epidemiol Biomarkers Prev, 2010. 19(1): p. 182-95.
53. Sponring, A., et al., Analysis of volatile organic compounds (VOCs) in the headspace of NCI-H1666 lung cancer cells. Cancer Biomark, 2010. 7(3): p. 153-61.
54. Wang, C., et al., Exhaled volatile organic compounds as lung cancer biomarkers during one-lung ventilation. Scientific reports, 2014. 4: p. 7312-7312.
55. Jalali, M., et al., Oxidative Stress Biomarkers in Exhaled Breath of Workers Exposed to Crystalline Silica Dust by SPME-GC-MS. J Res Health Sci, 2016. 16(3): p. 153-161.
56. Dryahina, K., et al., Pentane and other volatile organic compounds, including carboxylic acids, in the exhaled breath of patients with Crohn’s disease and ulcerative colitis. Journal of Breath Research, 2017. 12(1): p. 016002.
57. Lopes-Pacheco, M., E. Bandeira, and M.M. Morales, Cell-Based Therapy for Silicosis. Stem cells international, 2016. 2016: p. 5091838-5091838.
58. Mochalski, P., et al., Release and uptake of volatile organic compounds by human hepatocellular carcinoma cells (HepG2) in vitro. Cancer Cell International, 2013. 13(1): p. 72.
59. Koh, Y., et al., Comparative evaluation of software for retention time alignment of gas chromatography/time-of-flight mass spectrometry-based metabonomic data. Journal of Chromatography A, 2010. 1217(52): p. 8308-8316.
60. de Lacy Costello, B., et al., A review of the volatiles from the healthy human body. J Breath Res, 2014. 8(1): p. 014001.
61. Orellana, E.A. and A.L. Kasinski, Sulforhodamine B (SRB) Assay in Cell Culture to Investigate Cell Proliferation. Bio Protoc, 2016. 6(21).
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73464-
dc.description.abstract石英粉塵可以增加氧化壓力,脂質過氧化,並導致肺部纖維化之損傷。在之前我們的研究中對塵肺症勞工吐氣中的揮發性有機化合物進行分析,用於檢測塵肺症勞工的吐氣代謝變化。但塵肺症的內源性代謝揮發性生物標誌物仍然須被鑑定。本研究的目的是在確認石英的細胞毒性作用後,分析損傷肺泡上皮細胞頂空中的代謝物來探討可能的生物標誌物。我們在石英處理的人肺泡上皮細胞中進行了體外細胞培養實驗。本研究中使用的石英首先通過能量色散光譜掃描式電子顯微鏡確認其物理和化學性質。將A549人肺泡上皮細胞暴露於50, 100, 200, 500和1000 μg/mL的石英24, 48, 72小時,並通過LDH測量細胞膜損傷,8-isoprostane測定氧化壓力,以及透過IL-6測定發炎反應。當存在劑量反應關係時,我們確定了細胞毒性的存在並使用氣相層析質譜儀分析細胞頂空中的揮發性有機化合物。實驗結果顯示,檢測100顆石英的平均直徑為2.3μm。當暴露劑量大於或等於200 μg/mL以及暴露時間大於24小時,毒性作用顯著增加。基於細胞毒性研究的結果,我們分析了當細胞暴露200, 500和1000 μg/mL的石英24小時後的頂空氣體。損傷細胞產生辛烷、3,3-二甲基辛烷、2-甲基2-丙醇和2,3-二甲基庚烷四種有劑量反應關係的揮發性有機化合物,可能是塵肺症的潛在內源性的生物偵測指標。未來仍有必要進行動物實驗或流行病學前瞻性研究,以驗證生物標誌物可以在臨床應用上將塵肺症患者與健康人區分開來。zh_TW
dc.description.abstractQuartz dust can increase oxidative stress, lipid peroxidation, and cause pulmonary fibrosis. Analysis of volatile organic compounds (VOCs) in breath had been used to detect the metabolomics changes in pneumoconiosis patients. Potential metabolic VOCs biomarkers in pneumoconiosis are waiting to be identified. The objective of this study was to analyse endogenous VOCs in the headspace of injury cells after confirmed the cytotoxic effects of quartz. We conducted an in vitro study in quartz-treated human alveolar epithelial cells. Quartz used in this study was first examined by scanning electron microscopy with energy dispersive spectroscopy to confirm the physical and chemical properties. We exposed human alveolar A549 cell lines to 50, 100, 200, 500 and 1000 μg/mL of quartz for 24, 48, 72 hours, and measured the cell membrane damage by LDH assay, generation of reactive oxidative stress by 8-isoprostane assay, and inflammatory reaction by the interleukin-6 assay. We determined the existence of cytotoxicity when a dose-response relationship existed. When the cytotoxic effects were confirmed, we then analyzed the VOCs in the headspace of cells using gas chromatography-mass spectrometry (GC-MS). In our results, the mean diameter of quartz was 2.3 μm. The toxicity effects were significantly increased when the exposure dose was greater or equal to 200, 500 and 1000 μg/ mL and 24 hours. Based on the results of the cytotoxicity study, we analyzed the VOCs when cells were exposed to quartz at the concentration of 200 μg/mL for 24 hours. The injury cells generated octane, octane, 3,3-dimethyl-, 2-propanol, 2-methyl- and heptane, 2,3-dimethyl- of VOCs that might be potential volatile metabolites of pneumoconiosis. An in vivo study and prospective independent epidemiology study is warranted to validate the biomarkers could distinguish pneumoconiosis patients from healthy before clinical application.en
dc.description.provenanceMade available in DSpace on 2021-06-17T07:36:24Z (GMT). No. of bitstreams: 1
ntu-108-R05841016-1.pdf: 3181090 bytes, checksum: 8d2132fee37cb57349b26d4b0773c710 (MD5)
Previous issue date: 2019
en
dc.description.tableofcontents中文摘要 I
Abstract II
1.1 Introduction 1
1.2 Methods 3
1.2.1. To measure the background VOCs in the GC column, SPME fiber coating, glove box, and flask 4
1.2.2. Preparation of quartz 4
1.2.3. To determine the exposure time and dose 5
1.2.4. To explore the potential volatile biomarkers of lung cell injury 7
1.3 Results 14
1.4 Discussion 16
1.5 Conclusions 20
Tables 21
Table 1. Factor loading value of PC1, PC2 and PC3 from PCA. 21
Table 2. The difference between exposed quartz and unexposed A549 cell lines. 28
Figures 37
Figure 1. Preparation and analyses of particles. 37
Figure 2. Cytotoxicity studies of LDH cytotoxicity. 38
Figure 3. Cytotoxicity studies of oxidative stress. 39
Figure 4. Cytotoxicity studies of inflammation. 40
Figure 5. Heat map from exposed quartz and unexposed A549 cell lines. 41
Figure 6. PCA of the VOCs from exposed quartz and unexposed A549 cell lines. 43
Figure 7. Bar chart that summaries the VOCs that have dose-response relationships with quartz exposure. 44
Figure 8. Potential volatile biomarkers from exposed quartz and A549 cell lines. 45
References 46
Appendix 49
Appendix Table 1. MZmine parameters and optimized values for GC-MS data 49
Appendix Table 2. the 107 volatile metabolomics from lung injury cells 51
Appendix Figure 1. Reduce extraction environment interference. 59
Appendix Figure 2. Preparation of quartz. 60
Appendix Figure 3. Background of culture A549 cell lines. 61
Appendix Figure 4. Flow chart of cell headspace analysis by glass flasks. 62
Appendix Figure 5. To identify the endogenous biomarkers of VOCs. 63
Appendix Figure 6. centroid chromatographic data. 64
Appendix Figure 7. Results of instrument analysis. 64
Appendix Figure 8. Assessment of the SPME fiber blank. 65
Appendix Figure 9. Assessment of background air in the glove box. 66
Appendix Figure 10. Assessment of background air in the empty glass flask. 68
Appendix Figure 11. The cytotoxicity studies of cell viability test. 69
Appendix Figure 12. Assesse polystyrene empty flask source. 71
Appendix Figure 13. Flow chart of cell headspace analysis by polystyrene culture flasks. 73
Appendix Figure 14. Heat map of compounds by polystyrene culture flasks. 75
Appendix Figure 15. The principal component analysis by polystyrene culture flasks. 76
Appendix Figure 16. Establish a sterile cell culture environment using glass dishes. 77
dc.language.isoen
dc.subject石英zh_TW
dc.subject揮發性有機化合物zh_TW
dc.subject氧化壓力zh_TW
dc.subject體外細胞研究zh_TW
dc.subject氣相層析質譜儀zh_TW
dc.subjectquartzen
dc.subjectvolatile organic compounds (VOCs)en
dc.subjectoxidative stressen
dc.subjectin vitro studyen
dc.subjectgas chromatography-mass spectrometry (GC-MS)en
dc.title粉塵暴露引起肺部細胞損傷之揮發性代謝組學研究zh_TW
dc.titleVolatile metabolomics study on lung cell injury caused by dust exposureen
dc.typeThesis
dc.date.schoolyear107-2
dc.description.degree碩士
dc.contributor.oralexamcommittee陳保中(Pau-Chung Chen),鄭尊仁(Tsun-Jen Cheng),莊校奇(Hsiao-Chi Chuang),賴錦皇(Ching-Huang Lai)
dc.subject.keyword石英,揮發性有機化合物,氧化壓力,體外細胞研究,氣相層析質譜儀,zh_TW
dc.subject.keywordquartz,volatile organic compounds (VOCs),oxidative stress,in vitro study,gas chromatography-mass spectrometry (GC-MS),en
dc.relation.page77
dc.identifier.doi10.6342/NTU201900702
dc.rights.note有償授權
dc.date.accepted2019-04-15
dc.contributor.author-college公共衛生學院zh_TW
dc.contributor.author-dept職業醫學與工業衛生研究所zh_TW
顯示於系所單位:職業醫學與工業衛生研究所

文件中的檔案:
檔案 大小格式 
ntu-108-1.pdf
  未授權公開取用
3.11 MBAdobe PDF
顯示文件簡單紀錄


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。

社群連結
聯絡資訊
10617臺北市大安區羅斯福路四段1號
No.1 Sec.4, Roosevelt Rd., Taipei, Taiwan, R.O.C. 106
Tel: (02)33662353
Email: ntuetds@ntu.edu.tw
意見箱
相關連結
館藏目錄
國內圖書館整合查詢 MetaCat
臺大學術典藏 NTU Scholars
臺大圖書館數位典藏館
本站聲明
© NTU Library All Rights Reserved