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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 吳焜裕(Kuen-Yuh Wu) | |
dc.contributor.author | Yu-Syuan Luo | en |
dc.contributor.author | 羅宇軒 | zh_TW |
dc.date.accessioned | 2021-06-17T00:19:40Z | - |
dc.date.available | 2013-09-17 | |
dc.date.copyright | 2012-09-17 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-06-26 | |
dc.identifier.citation | Chapter I
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S. and H. H. Schaumburg (1974). 'A review of acrylamide neurotoxicity. Part II. Experimental animal neurotoxicity and pathologic mechanisms.' Can J Neurol Sci 1(3): 152-169. Tareke, E., T. M. Heinze, et al. (2009). 'Acrylamide formed at physiological temperature as a result of asparagine oxidation.' J Agric Food Chem 57(20): 9730-9733. Tareke, E., B. Lyn-Cook, et al. (2008). 'Acrylamide: a dietary carcinogen formed in vivo?' J Agric Food Chem 56(15): 6020-6023. Tareke, E., P. Rydberg, et al. (2002). 'Analysis of acrylamide, a carcinogen formed in heated foodstuffs.' J Agric Food Chem 50(17): 4998-5006. Torto, N. (2009). 'A Review of Microdialysis Sampling Systems.' Chromatographia 70(9-10): 1305-1309. Tsai, T. H., Y. F. Chen, et al. (1999). 'Measurement of unbound caffeic acid in rat blood by on-line microdialysis coupled with liquid chromatography and its application to pharmacokinetic study.' J Chromatogr B Biomed Sci Appl 729(1-2): 119-125. Twaddle, N. C., L. P. McDaniel, et al. (2004). 'Determination of acrylamide and glycidamide serum toxicokinetics in B6C3F(1) mice using LC-ES/MS/MS.' Cancer Lett 207(1): 9-17. USEPA (2010). Toxicological review of acrylamide. In Support of Summary Information on the Integrated Risk Information System (IRIS). Washington, DC, U.S Environmental Protection Agency: 4. WHO (2002). Health implications of acrylamide in food : report of a joint FAO/WHO consultation. Geneva, Switzerland, World Health Organization. ChapterII 1. Borgstrom, L.; Kagedal, B.; Paulsen, O., Pharmacokinetics of N-acetylcysteine in man. Eur J Clin Pharmacol 1986, 31 (2), 217-22. 2. IARC Acrylamide. Monographs on the evaluation of carcinogen risk to humans.; International Agency for Research on Cancer: Lyon, France, 1994; pp 389-433. 3. Tareke, E.; Rydberg, P.; Karlsson, P.; Eriksson, S.; Tornqvist, M., Analysis of acrylamide, a carcinogen formed in heated foodstuffs. J Agric Food Chem 2002, 50 (17), 4998-5006. 4. Tareke, E.; Heinze, T. M.; Gamboa da Costa, G.; Ali, S., Acrylamide formed at physiological temperature as a result of asparagine oxidation. J Agric Food Chem 2009, 57 (20), 9730-3. 5. WHO FAO/WHO Consultation on the Health Implications of Acrylamide in Food World Health Organization: Geneva, 25-27 June, 2002. 6. Settels, E.; Bernauer, U.; Palavinskas, R.; Klaffke, H. S.; Gundert-Remy, U.; Appel, K. E., Human CYP2E1 mediates the formation of glycidamide from acrylamide. Arch Toxicol 2008, 82 (10), 717-727. 7. Solomon, J. J., Cyclic adducts and intermediates induced by simple epoxides. IARC Sci Publ 1999, (150), 123-35. 8. Pernice, R.; Hauder, J.; Koehler, P.; Vitaglione, P.; Fogliano, V.; Somoza, V., Effect of sulforaphane on glutathione-adduct formation and on glutathione_S_transferase-dependent detoxification of acrylamide in Caco-2 cells. Mol Nutr Food Res 2009, 53 (12), 1540-1550. 9. March, J., Advanced organic chemistry : reactions, mechanisms, and structure. 4th ed.; Wiley: New York, 1992; p xv, 1495 p. 10. Sugiyama, S.; Ohigashi, S.; Sawa, R.; Hayashi, H., Selective Preparation of 2,3-Epoxypropanamide and Its Facile Conversion to 2,3-Dihydroxypropanamide with Acidic Resins. B Chem Soc Jpn 1989, 62 (10), 3202-3206. 11. (a) Sumner, S. C. J.; Macneela, J. P.; Fennell, T. R., Characterization and Quantitation of Urinary Metabolites of [1,2,3-C-13]Acrylamide in Rats and Mice Using C-13 Nuclear-Magnetic-Resonance Spectroscopy. Chem Res Toxicol 1992, 5 (1), 81-89; (b) Sumner, S. C.; Williams, C. C.; Snyder, R. W.; Krol, W. L.; Asgharian, B.; Fennell, T. R., Acrylamide: a comparison of metabolism and hemoglobin adducts in rodents following dermal, intraperitoneal, oral, or inhalation exposure. Toxicol Sci 2003, 75 (2), 260-70; (c) Hartmann, E. C.; Boettcher, M. I.; Bolt, H. M.; Drexler, H.; Angerer, J., N-Acetyl-S-(1-carbamoyl-2-hydroxy-ethyl)-l-cysteine (iso-GAMA) a further product of human metabolism of acrylamide: comparison with the simultaneously excreted other mercaptuic acids. Arch Toxicol 2009, 83 (7), 731-734; (d) Hartmann, E. C.; Latzin, J. M.; Schindler, B. K.; Koch, H. M.; Angerer, J., Excretion of 2,3-dihydroxy-propionamide (OH-PA), the hydrolysis product of glycidamide, in human urine after single oral dose of deuterium-labeled acrylamide. Arch Toxicol 2010; (e) Fuhr, U.; Boettcher, M. I.; Kinzig-Schippers, M.; Weyer, A.; Jetter, A.; Lazar, A.; Taubert, D.; Tomalik-Scharte, D.; Pournara, P.; Jakob, V.; Harlfinger, S.; Klaassen, T.; Berkessel, A.; Angerer, J.; Sorgel, F.; Schomig, E., Toxicokinetics of acrylamide in humans after ingestion of a defined dose in a test meal to improve risk assessment for acrylamide carcinogenicity. Cancer Epidem Biomar 2006, 15 (2), 266-271; (f) Fennell, T. R.; Sumner, S. C. J.; Snyder, R. W.; Burgess, J.; Friedman, M. A., Kinetics of elimination of urinary metabolites of acrylamide in humans. Toxicol Sci 2006, 93 (2), 256-267. 12. Pernice, R.; Hauder, J.; Koehler, P.; Vitaglione, P.; Fogliano, V.; Somoza, V., Effect of sulforaphane on glutathione-adduct formation and on glutathione_S_transferase-dependent detoxification of acrylamide in Caco-2 cells. Mol Nutr Food Res 2009, 53 (12), 1540-1550. 13. Fulmer, G. R.; Miller, A. J. M.; Sherden, N. H.; Gottlieb, H. E.; Nudelman, A.; Stoltz, B. M.; Bercaw, J. E.; Goldberg, K. I., NMR Chemical Shifts of Trace Impurities: Common Laboratory Solvents, Organics, and Gases in Deuterated Solvents Relevant to the Organometallic Chemist. Organometallics 2010, 29 (9), 2176-2179 ChapterIII 1. Borgstrom, L.; Kagedal, B.; Paulsen, O., Pharmacokinetics of N-acetylcysteine in man. Eur J Clin Pharmacol 1986, 31 (2), 217-22. 2. IARC Acrylamide. Monographs on the evaluation of carcinogen risk to humans.; International Agency for Research on Cancer: Lyon, France, 1994; pp 389-433. 3. Tareke, E.; Rydberg, P.; Karlsson, P.; Eriksson, S.; Tornqvist, M., Analysis of acrylamide, a carcinogen formed in heated foodstuffs. J Agric Food Chem 2002, 50 (17), 4998-5006. 4. (a) Mottram, D. S.; Wedzicha, B. L.; Dodson, A. T., Acrylamide is formed in the Maillard reaction. Nature 2002, 419 (6906), 448-449; (b) Stadler, R. H.; Blank, I.; Varga, N.; Robert, F.; Hau, J.; Guy, P. A.; Robert, M. C.; Riediker, S., Acrylamide from Maillard reaction products. Nature 2002, 419 (6906), 449-450. 5. Tareke, E.; Heinze, T. M.; Gamboa da Costa, G.; Ali, S., Acrylamide formed at physiological temperature as a result of asparagine oxidation. J Agric Food Chem 2009, 57 (20), 9730-3. 6. WHO Health implications of acrylamide in food : report of a joint FAO/WHO consultation; World Health Organization: Geneva, Switzerland, 2002. 7. Settels, E.; Bernauer, U.; Palavinskas, R.; Klaffke, H. S.; Gundert-Remy, U.; Appel, K. E., Human CYP2E1 mediates the formation of glycidamide from acrylamide. Arch Toxicol 2008, 82 (10), 717-727. 8. (a) Baum, M.; Fauth, E.; Fritzen, S.; Herrmann, A.; Mertes, P.; Merz, K.; Rudolphi, M.; Zankl, H.; Eisenbrand, G., Acrylamide and glycidamide: genotoxic effects in V79-cells and human blood. Mutat Res-Gen Tox En 2005, 580 (1-2), 61-69; (b) Mei, N.; McDaniel, L. P.; Dobrovolsky, V. N.; Guo, X. Q.; Shaddock, J. G.; Mittelstaedt, R. A.; Azuma, M.; Shelton, S. D.; McGarrity, L. J.; Doerge, D. R.; Heflich, R. H., The Genotoxicity of Acrylamide and Glycidamide in Big Blue Rats. Toxicol Sci 2010, 115 (2), 412-421; (c) Ghanayem, B. I.; Witt, K. L.; El-Hadri, L.; Hoffler, U.; Kissling, G. E.; Shelby, M. D.; Bishop, J. B., Comparison of germ cell mutagenicity in male CYP2E1-null and wild-type mice treated with acrylamide: evidence supporting a glycidamide-mediated effect. Biol Reprod 2005, 72 (1), 157-63; (d) Paulsson, B.; Kotova, N.; Grawe, J.; Henderson, A.; Granath, F.; Golding, B.; Tornqvist, M., Induction of micronuclei in mouse and rat by glycidamide, genotoxic metabolite of acrylamide. Mutat Res-Gen Tox En 2003, 535 (1), 15-24; (e) Segerback, D.; Calleman, C. J.; Schroeder, J. L.; Costa, L. G.; Faustman, E. M., Formation of N-7-(2-carbamoyl-2-hydroxyethyl)guanine in DNA of the mouse and the rat following intraperitoneal administration of [14C]acrylamide. Carcinogenesis 1995, 16 (5), 1161-5. 9. Dixit, R.; Seth, P. K.; Mukhtar, H., Metabolism of Acrylamide into Urinary Mercapturic Acid and Cysteine Conjugates in Rats. Drug Metab Dispos 1982, 10 (2), 196-197. 10. (a) Boettcher, M. I.; Bolt, H. M.; Drexler, H.; Angerer, J., Excretion of mercapturic acids of acrylamide and glycidamide in human urine after single oral administration of deuterium-labelled acrylamide. Arch Toxicol 2006, 80 (2), 55-61; (b) Fennell, T. R.; Sumner, S. C. J.; Snyder, R. W.; Burgess, J.; Friedman, M. A., Kinetics of elimination of urinary metabolites of acrylamide in humans. Toxicol Sci 2006, 93 (2), 256-267; (c) Doerge, D. R.; Twaddle, N. C.; Boettcher, M. I.; McDaniel, L. P.; Angerer, J., Urinary excretion of acrylamide and metabolites in Fischer 344 rats and B6C3F(1) mice administered a single dose of acrylamide. Toxicol Lett 2007, 169 (1), 34-42; (d) Bjellaas, T.; Olstorn, H. B. A.; Becher, G.; Alexander, J.; Knutsen, S. H.; Paulsen, J. E., Urinary metabolites as biomarkers of acrylamide exposure in mice following dietary crisp bread administration or subcutaneous injection. Toxicol Sci 2007, 100 (2), 374-380. 11. Doerge, D. R.; Young, J. F.; McDaniel, L. P.; Twaddle, N. C.; Churchwell, M. I., Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats. Toxicol Appl Pharmacol 2005, 208 (3), 199-209. 12. Luo, Y. S., Synthesis and Characterization of Acrylamide Metabolites: Acrylamide-Glutathione Adduct (AA-GSH),Glycidamide-Glutathione Adducts (GA2-GSH, GA3-GSH) and Glyceramide. unpublished 2012. 13. Center for Drug Evaluation and Research (U.S.); Center for Veterinary Medicine (U.S.), Guidance for industry bioanalytical method validation. U.S. Dept. of Health and Human Services, Food and Drug Administration Center for Veterinary Medicine: Rockville, MD, 2001; p. 1 online resource (22 p.). http://purl.access.gpo.gov/GPO/LPS120397. 14. Latzin, J. M.; Schindler, B. K.; Weiss, T.; Angerer, J.; Koch, H. M., Determination of 2,3-dihydroxypropionamide, an oxidative metabolite of acrylamide, in human urine by gas chromatography coupled with mass spectrometry. Anal Bioanal Chem 2012, 402 (7), 2431-8. 15. Pelucchi, C.; Galeone, C.; Levi, F.; Negri, E.; Franceschi, S.; Talamini, R.; Bosetti, C.; Giacosa, A.; La Vecchia, C., Dietary acrylamide and human cancer. Int J Cancer 2006, 118 (2), 467-71. Chapter IV 1. Borgstrom, L.; Kagedal, B.; Paulsen, O., Pharmacokinetics of N-acetylcysteine in man. Eur J Clin Pharmacol 1986, 31 (2), 217-22. 2. IARC Acrylamide. Monographs on the evaluation of carcinogen risk to humans.; International Agency for Research on Cancer: Lyon, France, 1994; pp 389-433. 3. (a) Spencer, P. S.; Schaumburg, H. H., A review of acrylamide neurotoxicity. Part I. Properties, uses and human exposure. Can J Neurol Sci 1974, 1 (2), 143-50; (b) Spencer, P. S.; Schaumburg, H. H., A review of acrylamide neurotoxicity. Part II. Experimental animal neurotoxicity and pathologic mechanisms. Can J Neurol Sci 1974, 1 (3), 152-69. 4. (a) Tareke, E.; Rydberg, P.; Karlsson, P.; Eriksson, S.; Tornqvist, M., Analysis of acrylamide, a carcinogen formed in heated foodstuffs. J Agric Food Chem 2002, 50 (17), 4998-5006; (b) Tareke, E.; Rydberg, P.; Karlsson, P.; Eriksson, S.; Tornqvist, M., Acrylamide: a cooking carcinogen? Chem Res Toxicol 2000, 13 (6), 517-22. 5. (a) Stadler, R. H.; Blank, I.; Varga, N.; Robert, F.; Hau, J.; Guy, P. A.; Robert, M. C.; Riediker, S., Acrylamide from Maillard reaction products. Nature 2002, 419 (6906), 449-450; (b) Mottram, D. S.; Wedzicha, B. L.; Dodson, A. T., Acrylamide is formed in the Maillard reaction. Nature 2002, 419 (6906), 448-449. 6. WHO Health implications of acrylamide in food : report of a joint FAO/WHO consultation; World Health Organization: Geneva, Switzerland, 2002. 7. Bolger, P. M.; Leblanc, J. C.; Setzer, R. W., Application of the Margin of Exposure (MoE) approach to substances in food that are genotoxic and carcinogenic EXAMPLE: Acrylamide (CAS No. 79-06-1). Food Chem Toxicol 2010, 48, S25-S33. 8. Settels, E.; Bernauer, U.; Palavinskas, R.; Klaffke, H. S.; Gundert-Remy, U.; Appel, K. E., Human CYP2E1 mediates the formation of glycidamide from acrylamide. Arch Toxicol 2008, 82 (10), 717-727. 9. (a) Ghanayem, B. I.; Witt, K. L.; El-Hadri, L.; Hoffler, U.; Kissling, G. E.; Shelby, M. D.; Bishop, J. B., Comparison of germ cell mutagenicity in male CYP2E1-null and wild-type mice treated with acrylamide: evidence supporting a glycidamide-mediated effect. Biol Reprod 2005, 72 (1), 157-63; (b) Besaratinia, A.; Pfeifer, G. P., Genotoxicity of acrylamide and glycidamide. J Natl Cancer I 2004, 96 (13), 1023-1029; (c) Mei, N.; McDaniel, L. P.; Dobrovolsky, V. N.; Guo, X. Q.; Shaddock, J. G.; Mittelstaedt, R. A.; Azuma, M.; Shelton, S. D.; McGarrity, L. J.; Doerge, D. R.; Heflich, R. H., The Genotoxicity of Acrylamide and Glycidamide in Big Blue Rats. Toxicol Sci 2010, 115 (2), 412-421. 10. Dixit, R.; Seth, P. K.; Mukhtar, H., Metabolism of Acrylamide into Urinary Mercapturic Acid and Cysteine Conjugates in Rats. Drug Metab Dispos 1982, 10 (2), 196-197. 11. (a) Baum, M.; Fauth, E.; Fritzen, S.; Herrmann, A.; Mertes, P.; Merz, K.; Rudolphi, M.; Zankl, H.; Eisenbrand, G., Acrylamide and glycidamide: genotoxic effects in V79-cells and human blood. Mutat Res-Gen Tox En 2005, 580 (1-2), 61-69; (b) Doerge, D. R.; da Costa, G. G.; McDaniel, L. P.; Churchwell, M. I.; Twaddle, N. C.; Beland, F. A., DNA adducts derived from administration of acrylamide and glycidamide to mice and rats. Mutat Res-Gen Tox En 2005, 580 (1-2), 131-141; (c) Manjanatha, M. G.; Aidoo, A.; Shelton, S. D.; Bishop, M. E.; McDaniel, L. P.; Lyn-Cook, L. E.; Doerge, D. R., Genotoxicity of acrylamide and its metabolite glycidamide administered in drinking water to male and female Big Blue mice. Environ Mol Mutagen 2006, 47 (1), 6-17. 12. Tong, G. C.; Cornwelll, W. K.; Means, G. E., Reactions of acrylamide with glutathione and serum albumin. Toxicol Lett 2004, 147 (2), 127-131. 13. March, J., Advanced organic chemistry : reactions, mechanisms, and structure. 4th ed.; Wiley: New York, 1992; p xv, 1495 p. 14. (a) Boettcher, M. I.; Bolt, H. M.; Drexler, H.; Angerer, J., Excretion of mercapturic acids of acrylamide and glycidamide in human urine after single oral administration of deuterium-labelled acrylamide. Arch Toxicol 2006, 80 (2), 55-61; (b) Hartmann, E. C.; Latzin, J. M.; Schindler, B. K.; Koch, H. M.; Angerer, J., Excretion of 2,3-dihydroxy-propionamide (OH-PA), the hydrolysis product of glycidamide, in human urine after single oral dose of deuterium-labeled acrylamide. Arch Toxicol 2010; (c) Fennell, T. R.; Sumner, S. C. J.; Snyder, R. W.; Burgess, J.; Friedman, M. A., Kinetics of elimination of urinary metabolites of acrylamide in humans. Toxicol Sci 2006, 93 (2), 256-267; (d) Doerge, D. R.; Twaddle, N. C.; Boettcher, M. I.; McDaniel, L. P.; Angerer, J., Urinary excretion of acrylamide and metabolites in Fischer 344 rats and B6C3F(1) mice administered a single dose of acrylamide. Toxicol Lett 2007, 169 (1), 34-42; (e) Bjellaas, T.; Olstorn, H. B. A.; Becher, G.; Alexander, J.; Knutsen, S. H.; Paulsen, J. E., Urinary metabolites as biomarkers of acrylamide exposure in mice following dietary crisp bread administration or subcutaneous injection. Toxicol Sci 2007, 100 (2), 374-380. 15. Doerge, D. R.; Young, J. F.; McDaniel, L. P.; Twaddle, N. C.; Churchwell, M. I., Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats. Toxicol Appl Pharmacol 2005, 208 (3), 199-209. 16. Luo, Y. S., Synthesis and Characterization of Acrylamide Metabolites: Acrylamide-Glutathione Adduct (AA-GSH),Glycidamide-Glutathione Adducts (GA2-GSH, GA3-GSH) and Glyceramide. unpublished 2012. 17. Luo, Y. S., An On-line Column-Switching LC-MS/MS Method Coupled with Microdialysis Sampling Techinque for Acrylamide Metabonomics in Rat Blood. unpublished 2012. 18. Yale, C. E.; Torhorst, J. B., Critical bleeding and plasma volumes of the adult germfree rat. Lab Anim Sci 1972, 22 (4), 497-502. 19. Twaddle, N. C.; McDaniel, L. P.; da Costa, G. G.; Churchwell, M. I.; Belanda, F. A.; Doerge, D. R., Determination of acrylamide and glycidamide serum toxicokinetics in B6C3F(1) mice using LC-ES/MS/MS. Cancer Lett 2004, 207 (1), 9-17. 20. Barber, D. S.; Hunt, J. R.; Ehrich, M. F.; Lehning, E. J.; LoPachin, R. M., Metabolism, toxicokinetics and hemoglobin adduct formation in rats following subacute and subchronic acrylamide dosing. Neurotoxicology 2001, 22 (3), 341-53. 21. (a) Sumner, S. C.; Williams, C. C.; Snyder, R. W.; Krol, W. L.; Asgharian, B.; Fennell, T. R., Acrylamide: a comparison of metabolism and hemoglobin adducts in rodents following dermal, intraperitoneal, oral, or inhalation exposure. Toxicol Sci 2003, 75 (2), 260-70; (b) Sumner, S. C. J.; Macneela, J. P.; Fennell, T. R., Characterization and Quantitation of Urinary Metabolites of [1,2,3-C-13]Acrylamide in Rats and Mice Using C-13 Nuclear-Magnetic-Resonance Spectroscopy. Chem Res Toxicol 1992, 5 (1), 81-89; (c) Fuhr, U.; Boettcher, M. I.; Kinzig-Schippers, M.; Weyer, A.; Jetter, A.; Lazar, A.; Taubert, D.; Tomalik-Scharte, D.; Pournara, P.; Jakob, V.; Harlfinger, S.; Klaassen, T.; Berkessel, A.; Angerer, J.; Sorgel, F.; Schomig, E., Toxicokinetics of acrylamide in humans after ingestion of a defined dose in a test meal to improve risk assessment for acrylamide carcinogenicity. Cancer Epidem Biomar 2006, 15 (2), 266-271; (d) Hartmann, E. C.; Boettcher, M. I.; Bolt, H. M.; Drexler, H.; Angerer, J., N-Acetyl-S-(1-carbamoyl-2-hydroxy-ethyl)-l-cysteine (iso-GAMA) a further product of human metabolism of acrylamide: comparison with the simultaneously excreted other mercaptuic acids. Arch Toxicol 2009, 83 (7), 731-734; (e) Fennell, T. R.; Sumner, S. C.; Snyder, R. W.; Burgess, J.; Spicer, R.; Bridson, W. E.; Friedman, M. A., Metabolism and hemoglobin adduct formation of acrylamide in humans. Toxicol Sci 2005, 85 (1), 447-59. 22. Gabard, B.; Mascher, H., Endogenous plasma N-acetylcysteine and single dose oral bioavailability from two different formulations as determined by a new analytical method. Biopharm Drug Dispos 1991, 12 (5), 343-53. 23. Miller, M. J.; Carter, D. E.; Sipes, I. G., Pharmacokinetics of acrylamide in Fisher-344 rats. Toxicol Appl Pharmacol 1982, 63 (1), 36-44 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66035 | - |
dc.description.abstract | 丙烯醯胺(acrylamide)的潛在致癌性及廣泛地存在於高溫炒炸食品中,近年來對於丙烯醯胺的食品安全議題日益受到重視。研究指出,丙烯醯胺的潛在致癌性質主要來自於中間代謝物環氧丙醯胺(glycidamide),而丙烯醯胺及環氧丙醯胺會與體內的谷胱甘肽(glutathione)結合而去除毒性。本研究旨在建立體內微透析液相層析串聯是質譜儀方法同時分析Sprague-Dawley大鼠體內血中丙烯醯胺Phase I & II reactions所有代謝物:丙烯醯胺(AA)、環氧丙醯胺(GA)、環氧丙醯胺之水解產物2,3-羥基丙醯胺(glyceramide)及丙烯醯胺和環氧丙醯胺與谷胱甘肽的共價鍵結物(AA-GSH & GA-GSH)。這些結果可供給研究物種間代謝機制差異,以評估丙烯醯胺對於人體的致癌性。本研究經由腹腔注射法,麻醉後分別給予大鼠0.1 mg/kg及5 mg/kg的丙烯醯胺,藉微透析活體採樣技術,串連液相層析-三段四極柱質譜儀,並佐以管柱交替(column-switching)法即時定量丙烯醯胺代謝物隨時間的變化。在0.1 mg/kg 劑量下,AA及AA-GSH 的代謝反應速率常數分別為 0.26 及 0.23 hr-1;半衰期則分別為2.67及2.97 小時。在5 mg/kg 劑量下,AA、GA及AA-GSH的代謝反應速率常數分別為0.23、0.14及0.20 hr-1;半衰期則分別為2.97、4.90及3.52 小時。原型物AA、代謝後GA及AA-GSH各自分別占總劑量的86.1%、8% 及1%。本研究結果指出,腹腔注射下,SD大鼠血中之AA代謝主要以從AA到GA為主。 | zh_TW |
dc.description.abstract | Acrylamide is a potential human carcinogen and widely existed in high temperature processed foods. As a result, the long-term exposure of acrylamide on food safety issue has been concerned. Previous studies suggested that metabolic activation of acrylamide to glycidamide might be responsible for its genotoxicity. Meanwhile, acrylamide and glycidamide would be detoxified by glutathione transferase to acrylamide- and glycidamide-glutathione adducts, and glycidamide can be spontaneously hydrolyzed or detoxified by epoxide hydrolase to glyceramide. This study is aimed to reveal acrylamide metabonomics in blood of Sprague-Dawley rats, including acrylamide, glycidamide, glyceramide, acrylamide-glutathione adducts (AA-GSH), glycidamide-glutathione adducts(GA-GSH), with an automated in vivo microdialysis isotope-dilution solid-phase extraction LC-MS/MS method. Results from this study can provide critical quantitative information of acrylamide metabolism in SD rats. Anaesthetized rats were treated with acrylamide of 0.1mg/kg and 5mg/kg by I.P. injection, respectively. Real-time acrylamide metabolites were profiled with an automated isotope-dilution column-switching LC-MS/MS method. The elimination rate constant (ke) was 0.26 hr-1 for AA and 0.23 hr-1 for AA-GSH and the half life (T1/2) was 2.67 hr for AA and 2.97 hr for AA-GSH in rats treated with 0.1 mg/kg. Ke of AA, AA-GSH and GA were 0.23, 0.2 and 0.14 hr-1, and T1/2 were 2.97, 3.52 and 4.9 hr for AA, AA-GSH and GA in rats treated with 5 mg/kg, respectively. Estimated with their area under curve (AUC), the AA, GA and AA-GSH account for 86.1%, 8% and 1% , respectively. This study reveals that the majority of absorbed AA is metabolically activated to GA. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T00:19:40Z (GMT). No. of bitstreams: 1 ntu-101-R99841005-1.pdf: 2666218 bytes, checksum: 73980db7ef346ca5d752c79c4c404e95 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | Acknowledgment I
摘要 II Abstract III Contents V Tables VIII Figures IX Chapter I : Introduction 1.1 Acrylamide 1 1.2 Microdialysis 8 1.3 On-line column-switching LC-MS/MS system 12 1.4 Rationale 16 1.5 Study design 17 Tables and Figures 19 References 24 Chapter II: Synthesis and Characterization of Acrylamide Metabolites: Acrylamide-Glutathione Adduct (AA-GSH), Glycidamide-Glutathione Adducts (GA2-GSH, GA3-GSH) and Glyceramide 32 Abstract 33 1. Introduction 34 2. Materials and Methods 37 3. Results and Discussions 39 4. Conclusions 47 5. Acknowledgement 47 Tables and Figures 48 Reference 64 Chapter III: Development of an Automated in vivo Micordialysis Isotope-Dilution On-line Column-Switching LC-MS/MS Method for Continuously Profiling Metabolites 67 Abstract 68 1. Introduction 69 2. Materials and Methods 70 3. Results and discussions 75 4. Conclusions 81 Tables and Figures 82 References 89 Chapter IV : In vivo Monitoring Metabolite Profiles of Acrylamide 93 Abstract 94 1. Introduction 95 2. Materials and methods 97 3. Results and discussions 100 4. Conclusions 106 5. Acknowledgement 107 Figures and Tables 108 Reference 114 Chapter V: Conclusions and Recommendations 120 | |
dc.language.iso | en | |
dc.title | 監測活體內丙烯醯胺之代謝物指紋 | zh_TW |
dc.title | In vivo Monitoring Metabolite profiles of Acrylamide | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 鄭尊仁(Tsun-Jen Cheng),陳家揚(Chia-Yang Chen),林靖愉(Ching-Yu Lin),蔡東湖(Tung-Hu Tsai) | |
dc.subject.keyword | 丙烯醯胺,谷胱甘肽,毒物代謝體學,液相層析-三段四極柱質譜儀,微透析活體採樣, | zh_TW |
dc.subject.keyword | Acrylamide,Glutathione,Metabonomics,LC-MS/MS,In vivo microdialysis, | en |
dc.relation.page | 121 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-06-26 | |
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 |
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