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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 羅翊禎 | |
| dc.contributor.author | Chih-Chuan Chang | en |
| dc.contributor.author | 張志銓 | zh_TW |
| dc.date.accessioned | 2021-06-16T16:11:57Z | - |
| dc.date.available | 2015-03-15 | |
| dc.date.copyright | 2013-03-15 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-02-18 | |
| dc.identifier.citation | Acharya, S., Wilson, T., Gradia, S., Kane, M.F., Guerrette, S., Marsischky, G.T.,
Kolodner, R., Fishel, R. hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6. Proc Natl Acad Sci U S A. 1996, 93, 13629-13634. Akingbemi, B.T.; Ge, R.; Klinefelter, G.R.; Zikrin, B.R.; Hardy, M.P. Phthalate induced Leydig cell hyperplasia is associated with multiple endocrine disturbances. Proc. Natl Acad. Sci. 2004, 101, 775–780. Akingbemi, B. T.; Sottas, C. M.; Koulova, A. I.; Klinefelter, G. R.; Hardy, M. P. Inhibition of testicular steroidogenesis by the xenoestrogen bisphenol A is associated with reduced pituitary luteinizing hormone secretion and decreased steroidogenic enzyme gene expression in rat leydig cells. Endocrinology. 2004, 145, 592-603. Akingbemi, B. T.; Youker, R. T.; Sottas, C. M.; Ge, R.; Katz, E.; Klinefelter, G. R.; Zirkin, B. R.; Hardy, M. P. Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl)phthalate. Biol. Reprod. 2001, 65(4), 1252-1259. Alani, E. The Saccharomyces cerevisiae Msh2 and Msh6 proteins form a complex that specifically binds to duplex oligonucleotides containing mismatched DNA base pairs. Mol Cell Biol. 1996, 16, 5604-5615. Alou, A. H., Jean, M., Domingue, O., Belzile, F. J. Structure and expression of AtPMS1, the Arabidopsis ortholog of the yeast DNA repair gene PMS1. Plant Science. 2004, 167, 447-456. Arcadi, F. A.; Costa, C.; Imperatore, C.; Marchese, A.; Rapisardi, A.; Salemi, M.; Trimarchi, G. R.; Costa, G. Oral toxicity of bis(2-ethylhexyl)phthalate during pregnancy and suckling in the Long-Evans rat. Food Chem. Toxicol. 1998, 35, 963-970. Bergink, S., and Jentsch, S. Principles of ubiquitin and SUNO modifications in DNA repair. Nature. 2009, 458, 461-467. Borstel, R. C. V., Quah, S. K., Steinber, Cm., Flury, F., Gottlieb, D. J. Mutants of yeast with enhanced spontaneous mutation rates. Genetics. 1973, 73, 141-151. Brechard, S.; Melchior, C.; Plancon, S.; Schenten, V.; Tschirhart, E. J. Store-operated Ca2+ channels formed by TRPC1, TRPC6 and Orai1 and non-store operated channels formed by TRPC3 are involved in the regulation of NADPH oxidase in HL-60 granulocytes. Cell Calcium. 2008, 44, 492–506. Burdett, V., Baitinger, C., Viswanathan, M., Lovett, S. T., Modrich, P. In vivo requirement for RecJ, ExoVII, ExoI, and ExoX in methyl-directed mismatch repair. Proceedings of the National Academy of Science of the United States of America. 2001, 98, 6765-6770. Cao, X. L.; Phthalate esters in foods: sources, occurrence, and analytical methods. Compr. Rev. Food Sci. Food Saf. 2010, 9, 21–45. Chandrasekaran, Y.; Richburg, J. H. The p53 protein influences the sensitivity of testicular germ cells to mono-(2-ethylhexyl) phthalate-induced apoptosis by increasing the membrane levels of fas and DR5 and decreasing the intracellular amount of c-FLIP. Biol. Reprod. 2005, 72(1), 206-213. Cheng, H.F.; Chen, S.Y.; Lin, J. G. Hazardous organic matters in municipal sewage sludge in Taiwan. Water Sci. Technol. 2001, 44(10), 65-70. Cheok, C. F., Bachrati, C. Z., Chan, K. L., Ralf, C., Wu, L. and Hickson1, D. I. Roles of the Bloom’s syndrome helicase in the maintenance of genome stability. Biochem Soc Trans. 2005, 33, 1456-1459. Cobellis, L.; Latini, G.; Felice, C. D.; Razzi, S.; Paris, I.; Ruggieri, F.; Mazzeo, P.; Petraglia, F. High plasma concentrations of di-(2-ethylhexyl)-phthalate in women with endometriosis. Human reproduction. 2003, 18(7), 1512-1515. Cooper, D. L., Lahue, R. S., Modrich, P. Methyl-directed mismatch repair is bidirectional. Journal of Biological Chemistry. 1993, 268, 11823-11829. Costanzo, M. C., Hogan, J. D., Cusick, M. E., Davis, B. P., Fancher, A. M., Hodges, P. E., Kondu, P., Lengieza, C., Lew-Smith, J. E., Lingner, C., et al. The yeast proteome database(YPD) and Caenorhabditis elegans proteome database(WormPD): comprehensive resources for the organization and comparison of model organism protein information. Nucleic Acids Res. 2000, 28, 73-76. Culligan, K. M., and Hays, J. B. Arabidopsis MutS homologs-AtMSH2, AtMSH3, AtMSH6, and a novel AtMSH7-form three distinct protein heterodimers with different specificities for mismatched DNA. Plant Cell. 2000, 12, 991-1002. Drummondm, J. T., Li, G.M., Longley, M.J., Modrich, P. Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells. Science. 1995, 268, 1909-1912. Duty, S.M.; Singh, N.P.; Silva, M.J.; Barr, D. B.; Brock, J.W.; Ryan, L.; Herrick, R. F.; Christiani, D. C.; Hauser, R. The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay. Environmental Health Perspectives. 2003, 111, 1164-1169. Enomoto, T. Functions of RecQ family helicases: possible involvement of Bloom's and Werner's syndrome gene products in guarding genome integrity during DNA replication. J Biochem. 2001, 9(3), 331-344. Erkekoglu, P.; Rachidi, W.; Yuzugullu, O. G.; Giray, B.; Favier, A.; Ozturk, M.; Hincl, F. Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium. Toxicol. Appl. Pharmacol. 2010, 248, 52-62. Fisher J. S. Are all EDC effects mediated via steroid hormone receptors? Toxicology. 2004, 205, 33-41. Fisher, J. S. Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome. Reproduction. 2004, 127, 305-315. Fisher, J. S.; Macpherson, S.; Marchetti, N.; Sharpe, R. M. Human 'testicular dysgenesis syndrome':a possible model using in utero exposure of the rat to dibutyl phthalate. Hum Reprod. 2003, 18(7), 1383-1394. Frederiksen, H.; Skakkebaek, N. E.; Andersson, A. M. Metabolism of phthalates in humans. Mol. Nutr. Food Res. 2007, 51, 899–911. Fridovich-Keil, J. L. Yeast as a model for human disease. Encyclopedia Of Life Science. 2005. Gang, Wanga., Jing, Pana., Sheng-Di, Chen. Kinases and kinase signaling pathways: Potential therapeutic targets in Parkinson's disease. Progress in Neurobiology. 2012, 98, 207-221. Genschel, J., Bazemore, L.R., Modrich, P. Human exonuclease I is required for 5' and 3' mismatch repair. Journal of Biological Chemistry. 2002, 277, 13302-13311. Gesler, R. M. Toxicology of Di-2-ethylhexyl Phthalate and other phthalic acid Ester plasticizers. Environmental Health Perspectives.1973, 73-9. Ghosh, J.; Das, J,; Manna, P,; Sil, P. C. Hepatotoxicity of di-(2-ethylhexyl)phthalate is attributed to calcium aggravation, ROS-mediated mitochondrial depolarization and ERK/NF-κB pathway activation. Free Radical Biology & Medicine. 2010, 49, 1779-1791. Goffeau, A., Barrell, B. G., Bussey, H., Davis, R. W., Dujon, B., Feldmann, H., Galibert, F., Hoheisel, J. D., Jacq, C., Johnston, M., et al. Life with 6000 genes. Science. 1996, 274, 546, 563-547. Grasso, P.; Heindel, J.; Powell, C.; Reichert, J. L. Effects of mono(2-ethylhexyl) phthalate, a testicular toxicant, on follicle-stimulating hormone binding to membranes from cultured rat Sertoli cells. Biol Reprod. 1993, 48, 454-9. Gray, L.E.; Ostby, J.; Furr, J.; Price, M.; Veeramachaneni, D. N.; Parks, L. Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol Sci. 2000, 58(2), 350-365. Greene, C.N., JinksRobertson, S. Frameshift intermediates in homopolymer runs are moved efficiently by yeast mismatch repair proteins. Molecular and Cellular Biology. 1997, 17, 2844-2850. Guo, S., Presnell, S.R., Yuan, F., Zhang, Y., Gu, L., Li, G.M. Differential requirement for proliferating cell nuclear antigen in 5' and 3' nick-directed excision in human mismatch repair. Journal of Biological Chemistry. 2004, 279, 16912-16917. Hanada, K., Budzowska, M., Modesti, M., Maas, A., Wyman, C., Essers, J., Kanaar, R. The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks. EMBO J. 2006, 25, 4921-4932. Hauser, R. J. D.; Meeker, N.P.; Singh, et al. DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Human Reproduction. 2007, 22, 688-795. Hsieh, P., and Yamane, K. DNA mismatch repair: molecular mechanism, cancer, and ageing. Mechanism of ageing and development. 2008, 123, 391-407. Iyer, R. R., Pluciennik, A., Burdett, V., Modrich P.L. DNA mismatch repair: Functions and mechanisms. Chemical Reviews. 2006, 106, 302-323. Jacob, S., Praz, F. DNA mismatch repair defects: role in colorectal carcinogenesis. Biochimie. 2002, 84, 27-47. Kavlock, R. J. Research needs for risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop. Environmental Health Perspectives. 1996, 104:715-40. Kavlock, R.; Boeckelheide, K.; Chapin, R.; Cunningham, M.; Faustman, E.; Foster, P. et al. NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di(2-ethylhexyl)phthalate. Reprod. Toxicol. 2002, 16, 529-653. Koch, H.; Rossbach B.; Drexler H.; Angerer J. Internal exposure of the general population to DEHP and other phthalates determination of secondary and primary phthalate monoester metabolites in urine. Environmental Res. 2003, 93, 177-185. Koch, H. M.; Preuss, R.; Angerer, J. Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure – an update and latest results. International journal of andrology. 2006, 29, 155-65. Koch, H.M.; Preuss, R.; Drexler, H.; Angerer, J. Exposure of nursery school children and their parents and teachers to di-n-butylphthalate and butylbenzylphthalate. International archives of occupational and environmental health. 2005, 78(3), 223-229. Kolodner, R. Biochemistry and genetics of eukaryotic mismatch repair. Genes Dev. 1996, 10, 1433-1442. Kunkel, T. A., Erie, D. A. DNA mismatch repair. 2005, 74, 681-710. Kurz, E. U., Lees-Miller, S. P. DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA Repair (Amst). 2004, 3, 889-900. Lahue, R. S., Modrich, P. DNA mismatch correction in a defined system. Science. 1989, 245, 160-164. Latini, G. Monitoring phthalate exposure in humans. Clinica chimica acta; international journal of clinical chemistry. 2005, 361(1-2), 20-9. Latini, G.; Felice, C. D.; Presta, G.; Vecchio, A. D.; Paris, I.; Ruggieri, F.; Mazzeo, P. In Utero Exposure to Di-(2-ethylhexyl)phthalate and duration of human pregnancy. Environmental Health Perspectives. 2003, 111, 1783-1785. Lin, C. H.; Chen, T. J.; Chen, S. S.; Hsiao, P.C.; Yang, R. C. Activation of Trim17 by PPARγ is involved in Di(2-ethylhexyl) phthalate (DEHP)-induced apoptosis on Neuro-2a cells. Toxicol. Lett. 2011, 206, 245-251. Lorz, P.; Towae F,; Enke W,; Jackh R,; Bhargava N.; Phthalic acid and derivatives. Ullmann's encyclopedia of industrial chemistry 2002;Weinheim(Wiley-VCH). Lovekamp-Swan, T.; Davis, B. J. Mechanisms of phthalate ester toxicity in the female reproductive system. Environmental Health Perspectives. 2003, 111(2), 139-45. Mankouri, H. W., and Hickson, I. D. Understanding the roles of RecQ helicases in the maintenance of genome integrity and suppression of tumorigenesis. Biochem Soc Trans. 2004, 32, 957-958 Marsischky, G.T., Filosi, N., Kane, M. F., and Kolodner, R. Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Genes & Dev. 1996, 10, 407-420. McKee, R. H. The role of inhibition of gap junctional intercellular communication in rodent liver tumor induction by phthalates: review of data on selected phthalates and the potential relevance to man. Regul. Toxicol. Pharmacol. 2000, 32, 51–55. Moore, R. W.; Rudy, T. A.; Lin, T. M.; Ko, K.; Peterson, R. E. Abnormalities of sexual development in male rats with in utero and lactational exposure to the antiandrogenic plasticizer Di(2-ethylhexyl) phthalate. Environ. Health Perspect. 2001, 109(3), 229-237. Mountain, H. A., Bystrom, A. S., Larsen, J. T., Korch, C. 4 Major transcriptional responses in the methionine threonine biosynthetic-pathway of Saccharomyces cerevisiae. Yeast. 1991, 7, 781-803 Mylchreest, E.; Foster, P. M. DBP exerts its antiandrogenic activity by indirectly interfering with androgen signalling pathways. Toxicol Appl Pharmacol. 2000, 168, 174-175. Mylchreest, E.; Sar, M.; Wallace, D.G.; Foster, P. M. Fetal testosterone insufficiency and abnormal proliferation of Leydig cells and gonocytes in rats exposed to di(n-butyl) phthalate. Reproductive Toxicology. 2002, 16, 19-28. Niedernhofer, L.J., Odijk, H., Budzowska, M., van Drunen, E., Maas, A., Theil, A.F., de Wit, J., Jaspers, N.G., Beverloo, H.B., Hoeijmakers, J.H., Kanaar, R. The structure-specific endonuclease Ercc1-Xpf is required to resolve DNA interstrand cross-link-induced double-strand breaks. Mol Cell Biol. 2004, 24, 5776-5787. Niida, H., Nakanishi, M. DNA damage checkpoints in mammals. Mutagenesis. 2006, 21, 3-9. Nurse, P. A long twentieth century of the cell cycle and beyond. Cell. 2000, 121, 167-178. Oberdoerffer, P.; Sinclair, D. A. The role of nuclear architecture in genomic instability and ageing. Nat. Rev. Mol. Cell Biol. 2007, 8(9), 692-702. Parker, B. O., and Marinus, M. G. Repair of DNA heteroduplexes containing small heterologous sequences in Escherichia coli. Proceeding of the National Academy of Sciences of the United States of America. 1992, 89, 1730-1734. Park, J. D.; Habeebu, S. S. M.; Klaassen C. D. Testicular toxicity of di-(2-ethylhexyl) phthalate in young Sprague-Dawley rats. Toxicology. 2002, 171, 105-115. Parker, K. L. The roles of steroidogenicfactor1 in endocrinedevelopment and function. Mol Cell Endocrinol. 1998, 145, 15-20. Parks, L. G.; Ostby, J. S.; Lambright, C. R.; Abbott, B. D.; Klinefelter, G. R.; Barlow, N. J.; Gray, L. E. Jr. The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol. Sci. 2000, 58(2), 339-349. Petranovic, D., and Nielsen, J. Can yeast systems biology contribute to the understanding of human disease? Trend biotechnol. 2008, 26, 584-590. Robert, M., Gesler. Toxicology of di-2-ethylhexyl phthalate and other phthalic acid ester plasticizers. Environmental Health Perspectives. 1973, 73-79. Rogers, R.; Ouellet, M.; Brown, C.; Moyer, B.; Rasoulpour, T.; Hixon, M. Cross-talk between the Akt and NF-κB signaling pathways inhibits MEHP-induced germ cell apoptosis. Toxicol. Sci. 2008, 106, 497–508. Rosado-Berrios, C. A.; Velez, C.; Zayas, B. Mitochondrial permeability and toxicity of diethylhexyl and monoethylhexyl phthalates on TK6 human lymphoblasts cells. Toxicol. Vitro. 2011, 25, 2010-2016. Prolla, T.A., Pang, Q., Alani, E., Kolodner, R.D., Liskay, R.M. MLH1, PMS1, and MSH2 interactions during the initiation of DNA mismatch repair in yeast. Science. 1994, 265, 1091-1093. Schmidt, K. H., Pennaneach, V., Putnam, C. D., Kolodner, R. D. Analysis of gross-chromosomal rearrangement in Saccharomyces cerevisiae. DNA Repair. 2006, 409, 462-476. Silva, M.J.; Barr, D. B.; Reidy, J.A.; kato, k.; Malek, N. A.; Hodge, C. C.; Hurtz, D. Calafat, A. M.; Needham, L. L.; Brock, J. W. Glucuronidation patterns of common urinary and serum monoester phthalate metabolites. Arch Toxicol. 2003, 77, 561-7. Sinha A. K., Bhattach, J.K. Lysine biosynthesis in Saccharomyces conversion of alpha-aminiadipate into alpha-aminoadipic delta-semialdehyde. Biochemical Journal. 1971, 125, 743-&. Swan, S. H.; Main, K.M.; Liu, F.; Stewart, S. L.; Kruse, R. L.; Calafat, A.M.; Mao, C. S.; Redmon, J. B.; Ternand, C.L.; Sullivan, S.; Teague, J. L. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environmental Health Perspectives. 2005, 113(8), 1056-1061. Sharpe, R. M.; Hormones and testis development and the possible adverse effects of environmental chemicals. Toxicology letters. 2001, 120, 221-232. Shea, K. M. Pediatric exposure and potential toxicity of phthalate plasticizers. Pediatrics 2003, 111, 1467-1474. Soreide, K. Molecular testing for microsatellite instability and mismatch repair defects in hereditary and sporadic colorectal cancers- Ready for prime time? Tumor Biology. 2007, 55, 862-880. Strand, M., Prolla, T. A., Liskay, R. M., Petes, T. D. Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature. 1993, 365, 274-276. Thompson, C. J.; Ross, S. M.; Gaido, K. W. Di(n-butyl) phthalate impairs cholesterol transport and steroidogenesis in the fetal rat testis through a rapid and reversible mechanism. Endocrinology. 2004, 145, 1227-1237. Tomimatsu, N., Tahimic, C. G., Otsuki, A., Burma, S., Fukuhara, A., Sato, K., Shiota, G., Oshimura, M., Chen, D.J., Kurimasa, A. Ku70/80 modulates ATM and ATR signaling pathways in response to DNA double strand breaks. J Biol Chem. 2007, 282(14), 10138-1-145. Trachootham, D.; Alexandre, J.; Huang, P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nature Reviews Drug Discovery. 2009, 8, 579-591. Uziel, T., Lerenthal, Y., Moyal, L., Andegeko, Y., Mittelman, L., Shiloh, Y. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J. 2003, 22, 5612-5621. Van Attikum, H., and Gasser, S. M. The histone code at DNA breaks: a guide to repair? Nat Rev Mol Cell Biol. 2005, 6, 757-765. Wahl, H.G.; Hong, Q.; Hildenbrand, S.; Risler, T.; Luft, D.; Liebich, H. 4-Heptanone is a metabolite of the plasticizer di-(2-ethylhexyl) phthalate (DEHP) in haemodialysis patients. Nephrology, Dialysis, Transplantation. 2004, 19, 2576–2583. Watson, P., Butzow, R., Lynch, H. T., Mecklin, J. P., Jarvinen, H. J., Vasen, H. F. A., Madlensky, L., Fidalgo, P., Bernstein, I. The clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer. Gynecologic Oncology. 2001, 82, 223-228. Wu, S. Y., Culligan, K., Lamers, M., and Hays, J. Dissimilar mispair-recognition spectra of Arabidopsis DNA-mismatch-repair proteins MSH2•MSH6 (MutSα) and MSH2•MSH7 (MutSγ). Nucleic Acids Research. 2003, 31, 6027-6034. Yuan, S.Y.; Liu, C.; Liao, C.S.; Chang, B.V. Occurrence and microbial degradation of phthalate esters in Taiwan river sediments. Chemosphere. 2002, 49(10), 1295-9. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/62836 | - |
| dc.description.abstract | 塑化劑是種廣泛用於工業用途上的化合物，常被使用添加於塑膠製品中，而使用最普遍的則是一群稱為鄰苯二甲酸酯類的化合物。目前已知鄰苯二甲酸酯類是種環境賀爾蒙，會造成類似雌激素的作用，由動物實驗已知會造成生殖毒性、DNA損傷等，且在雄性子代中會造成隱睪症、尿道下裂症、不孕症和睪丸異常等生殖相關疾病。其他研究也指出在小鼠實驗發現，會造成其肝臟損傷以及過氧化體增生，造成致癌，且也發現會誘發氧化壓力產生及粒線體的功能缺失。然而，塑化劑對於動物體甚至於人體之基因穩定性及基因突變率的影響仍是未知的。因此，我們以酵母菌做為模式生物，探討塑化劑對細胞基因穩定性之影響。我們首先利用不同劑量的塑化劑dibutyl phthalate (DBP)和dimethyl phthalate (DMP)，將其溶解在液態培養液中與正常及錯誤配對基因剔除 (msh2Δ, msh3Δ, msh6Δ)的酵母菌共培養，觀察其不同天數的生長曲線和細胞存活率。而對於基因穩定性之影響則是藉由基因突變分析法 (CANr, Hom+, Lys+)觀察其突變率。結果顯示，塑化劑DBP及DMP對於正常及突變的酵母菌細胞的生長曲線皆有抑制效果，其中以最高濃度的DMP (5mM)最為顯著。而突變率分析試驗則是發現塑化劑DMP會造成msh6Δ突變株的酵母菌細胞之突變率顯著增加。而在ROS產生量方面，正常及突變細胞在加入塑化劑後，其過氧化氫及超氧陰離子的含量與控制組相比並無差異，但是對於正常細胞在加入DMP後，其過氧化氫量隨天數有顯著增加，此點與Lys+的結果相同。根據我們的研究，塑化劑對於正常細胞及突變細胞都會造成影響，且塑化劑會造成錯誤配對修復缺陷菌株之突變率增加，尤其以DMP會造成msh6Δ細胞株突變率有最明顯的上升，不過對於ROS的產生量，除了加入DMP的正常細胞外，其他組別並沒有顯著的影響。 | zh_TW |
| dc.description.abstract | Plasticizers are abundant compounds used in the manufacturing industry. Some are known as endocrine disruptors, such as xenoestrogens. Others induce reproductive toxicity and damage to DNA. It was shown to cause liver damage, peroxisome proliferation, and induce carcinogenesis in mouse. Animal studise also showed that DEHP caused oxidative stress, mitochondrial dysfunction and contributed phthalate-induced disruption of spermatogenesis. However, it is not known whether DEHP and other derivatives can cause genome instability, which is a hallmark of cancer. Thus, the objective of this study is to study the effect of DBP and DMP on genome stability using S. cerevisiae as a model. We treated yeast cells with various concentrations (0.05mM, 0.5mM, 5mM) of DBP and DMP determined cell growth and viabilities. Normal cells and DNA repair defective cells (msh2Δ, msh3Δ, msh6Δ) were cultured with DBP and DMP or without. Genome stability can be evaluated by measuring rates of gene mutation, including CANr, Hom+ and Lys+ mutation assays. Results showed that plasticizers inhibited cells growth and cell viabilities. Particularly, five milimole of DMP showed the most effective inhibition. We observed that DMP induced the highest mutation rate in msh6Δ cells compared to WT, msh2Δ and msh3Δ cells. There was no significant difference on ROS levels in cells treated with or without DBP and DMP. Our results suggest that DBP and DMP may have adverse effect on genome stability in mismatch repair defective cells. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T16:11:57Z (GMT). No. of bitstreams: 1 ntu-102-R99641018-1.pdf: 1839961 bytes, checksum: 8be09054bbd4bb423538d6e451aa30b0 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 誌謝................................................................i
摘要...............................................................ii Abstract............................................................iii 目錄...............................................................iv 圖目錄.............................................................vii 表目錄.............................................................ix 縮寫對照表...........................................................x 第一章、前言.........................................................1 第二章、文獻整理.....................................................2 第一節 鄰苯二甲酸酯類(Phthalates) ..............................2 一、鄰苯二甲酸酯類之結構.....................................3 二、鄰苯二甲酸酯類對動物的影響...............................6 三、鄰苯二甲酸酯類在人體之代謝...............................7 四、鄰苯二甲酸酯類對於人體造成之影響.........................9 第二節 鄰苯二甲酸酯類對動物體之影響機制.....................11 一、 鄰苯二甲酸酯類做為內分泌甘擾素影響賀爾蒙...............11 二、鄰苯二甲酸酯類對動物體影響之反應機制....................13 第三節 酵母菌 Saccharomyces cerevisiae可做為一良好模式生物.....17 一、酵母菌做為模式生物的優點................................18 二、與癌症發生相關的可能調控機制............................19 第四節 DNA修復............................................21 一、非同源黏合 (Non-homologous end joining, NHEJ) .............22 二、同源重組修復 (Homologous recombination, HR)...............23 三、鹼基切割修復 (Base-excision repair, BER)....................25 四、核甘酸切割修復 (Nucleotide-excision repair, NER).............25 五、複製後修復 (Post-replication repair, PRR).....................25 六、錯誤配對修復 (Mismatch repair, MMR)......................26 第五節、 錯誤配對修復 (MMR)...................................28 一、錯誤配對修復系統的修復機制..............................29 (I) DNA損傷部位確認....................................29 (II) DNA修復複合體之交互作用...........................31 (III) 新舊股之辨認......................................33 (IV) DNA股切割、合成與黏合.............................33 二、MMR系統缺陷與癌症之間的關係...........................34 第三章、實驗架構....................................................35 第四章、材料與方法..................................................36 第一節、實驗材料................................................36 一、酵母種類................................................36 二、培養液及培養皿..........................................37 三、Canavanine培養皿........................................38 四、Lys及Thr胺基酸剔除培養皿...............................39 五、塑化劑..................................................40 第二節、實驗儀器................................................41 第三節、實驗方法................................................42 一、酵母菌培養方式..........................................42 二、酵母菌生長曲線及存活率..................................42 三、突變率分析試驗..........................................43 四、活性態氧自由基測試......................................46 五、統計分析................................................46 第五章、結果與討論 第一節、不同種類及濃度的塑化劑對酵母菌生長曲線之影響............47 第二節、不同種類及濃度的塑化劑對酵母菌存活率之影響..............51 第三節、在塑化劑處理下對酵母菌基因突變率之影響..................54 一、Can耐受突變(Can forward mutation).........................54 二、Hom回復突變(Hom revertant mutation).......................57 三、Lys回復突變(Lys revertant mutation).........................59 第四節、塑化劑處理下對酵母菌ROS產生量之影響...................62 第六章、結論........................................................66 第七章、參考文獻....................................................68 | |
| dc.language.iso | zh-TW | |
| dc.title | 塑化劑對酵母菌基因穩定性之影響 | zh_TW |
| dc.title | The effect of plasticizer on genome stability in S. cerevisiae. | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 高承福,謝淑貞 | |
| dc.subject.keyword | 塑化劑,DNA損傷,氧化壓力,基因突變,錯誤配對修補, | zh_TW |
| dc.subject.keyword | plasticizer,DNA damage,oxidative stress,gene mutation,mismatch repair, | en |
| dc.relation.page | 94 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-02-18 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 食品科技研究所 | zh_TW |
| 顯示於系所單位： | 食品科技研究所 | |
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