請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42888
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 彭福佐(Fu-Chuo Peng) | |
dc.contributor.author | Sing-Yi Gu | en |
dc.contributor.author | 古幸宜 | zh_TW |
dc.date.accessioned | 2021-06-15T01:27:39Z | - |
dc.date.available | 2010-09-15 | |
dc.date.copyright | 2009-09-15 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-07-22 | |
dc.identifier.citation | Akopyan, G., and B. Bonavida. 2006. Understanding tobacco smoke carcinogen NNK and lung tumorigenesis. Int J Oncol. 29:745-52.
Alison, M.R., R. Poulsom, S. Forbes, and N.A. Wright. 2002. An introduction to stem cells. J Pathol. 197:419-23. ATSDR. 1990a. Toxicological Profile for Benzo(a)pyrene. Prepared by ICF-Clement, under Contract No. 68-02-4235. Baird, W.M., L.A. Hooven, and B. Mahadevan. 2005. Carcinogenic polycyclic aromatic hydrocarbon-DNA adducts and mechanism of action. Environ Mol Mutagen. 45:106-14. Binkova, B., Y. Giguere, P. Rossner, Jr., M. Dostal, and R.J. Sram. 2000. The effect of dibenzo[a,1]pyrene and benzo[a]pyrene on human diploid lung fibroblasts: the induction of DNA adducts, expression of p53 and p21(WAF1) proteins and cell cycle distribution. Mutat Res. 471:57-70. Blanton, R.H., M. Lyte, M.J. Myers, and P.H. Bick. 1986. Immunomodulation by polyaromatic hydrocarbons in mice and murine cells. Cancer Res. 46:2735-9. Bock, K.W., and C. Kohle. 2006. Ah receptor: dioxin-mediated toxic responses as hints to deregulated physiologic functions. Biochem Pharmacol. 72:393-404. Boers, J.E., A.W. Ambergen, and F.B. Thunnissen. 1999. Number and proliferation of clara cells in normal human airway epithelium. Am J Respir Crit Care Med. 159:1585-91. Buening, M.K., P.G. Wislocki, W. Levin, H. Yagi, D.R. Thakker, H. Akagi, M. Koreeda, D.M. Jerina, and A.H. Conney. 1978. Tumorigenicity of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides in newborn mice: exceptional activity of (+)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a ]pyrene. Proc Natl Acad Sci U S A. 75:5358-61. Bullock, A.N., and A.R. Fersht. 2001. Rescuing the function of mutant p53. Nat Rev Cancer. 1:68-76. Caino, M.C., J.L. Oliva, H. Jiang, T.M. Penning, and M.G. Kazanietz. 2007. Benzo[a]pyrene-7,8-dihydrodiol promotes checkpoint activation and G2/M arrest in human bronchoalveolar carcinoma H358 cells. Mol Pharmacol. 71:744-50. Carmichael, J., J.B. Mitchell, W.G. DeGraff, J. Gamson, A.F. Gazdar, B.E. Johnson, E. Glatstein, and J.D. Minna. 1988. Chemosensitivity testing of human lung cancer cell lines using the MTT assay. Br J Cancer. 57:540-7. Chang, L.H. 1943. The fecal excretion of polycyclic hydrocarbons following their administration to the rat. J. Biol. Chem. . 151:93-99. Chang, L.W., Y.C. Chang, C.C. Ho, M.H. Tsai, and P. Lin. 2007. Increase of carcinogenic risk via enhancement of cyclooxygenase-2 expression and hydroxyestradiol accumulation in human lung cells as a result of interaction between BaP and 17-beta estradiol. Carcinogenesis. 28:1606-12. Chuykin, I.A., M.S. Lianguzova, T.V. Pospelova, and V.A. Pospelov. 2008. Activation of DNA damage response signaling in mouse embryonic stem cells. Cell Cycle. 7:2922-8. Cohen, G.M. 1990. Pulmonary metabolism of foreign compounds: its role in metabolic activation. Environ Health Perspect. 85:31-41. Cosgrave, N., A.D. Hill, and L.S. Young. 2006. Growth factor-dependent regulation of survivin by c-myc in human breast cancer. J Mol Endocrinol. 37:377-90. Dang, C.V. 1999. c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol. 19:1-11. De Jong, W.H., E.D. Kroese, J.G. Vos, and H. Van Loveren. 1999. Detection of immunotoxicity of benzo[a]pyrene in a subacute toxicity study after oral exposure in rats. Toxicol Sci. 50:214-20. Demello, D.E., S. Mahmoud, J. Ryerse, and J.W. Hoffmann. 2002. Generation and characterization of a conditionally immortalized lung clara cell line from the H-2Kb-tsA58 transgenic mouse. In Vitro Cell Dev Biol Anim. 38:154-64. Dinis-Oliveira, R.J., F. Remiao, J.A. Duarte, R. Ferreira, A. Sanchez Navarro, M.L. Bastos, and F. Carvalho. 2006. P-glycoprotein induction: an antidotal pathway for paraquat-induced lung toxicity. Free Radic Biol Med. 41:1213-24. Fehrenbach, H., A. Fehrenbach, T. Pan, M. Kasper, and R.J. Mason. 2002. Keratinocyte growth factor-induced proliferation of rat airway epithelium is restricted to Clara cells in vivo. Eur Respir J. 20:1185-97. Giangreco, A., S.D. Reynolds, and B.R. Stripp. 2002. Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. Am J Pathol. 161:173-82. Guo, N., D.V. Faller, and C. Vaziri. 2000. A novel DNA damage checkpoint involving post-transcriptional regulation of cyclin A expression. J Biol Chem. 275:1715-22. Hecht, S.S. 1999. Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst. 91:1194-210. Hermans, C., and A. Bernard. 1999. Lung epithelium-specific proteins: characteristics and potential applications as markers. Am J Respir Crit Care Med. 159:646-78. Hockley, S.L., V.M. Arlt, D. Brewer, I. Giddings, and D.H. Phillips. 2006. Time- and concentration-dependent changes in gene expression induced by benzo(a)pyrene in two human cell lines, MCF-7 and HepG2. BMC Genomics. 7:260. Hong, K.U., S.D. Reynolds, A. Giangreco, C.M. Hurley, and B.R. Stripp. 2001. Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion. Am J Respir Cell Mol Biol. 24:671-81. Horton, J.K., J.C. Rosenior, J.R. Bend, and M.W. Anderson. 1985. Quantitation of benzo(a)pyrene metabolite: DNA adducts in selected hepatic and pulmonary cell types isolated from [3H]benzo(a)pyrene-treated rabbits. Cancer Res. 45:3477-81. Jeffy, B.D., E.J. Chen, J.M. Gudas, and D.F. Romagnolo. 2000. Disruption of cell cycle kinetics by benzo[a]pyrene: inverse expression patterns of BRCA-1 and p53 in MCF-7 cells arrested in S and G2. Neoplasia. 2:460-70. Ketkar, M., G. Reznik, P. Schneider, and U. Mohr. 1978. Investigations on the carcinogenic burden by air pollution in man. Intratracheal instillation studies with benzo(a)pyrene in bovine serum albumin in Syrian hamsters. Cancer Lett. 4:235-9. Kim, C.F., E.L. Jackson, A.E. Woolfenden, S. Lawrence, I. Babar, S. Vogel, D. Crowley, R.T. Bronson, and T. Jacks. 2005. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 121:823-35. Ko, Y.C., L.S. Cheng, C.H. Lee, J.J. Huang, M.S. Huang, E.L. Kao, H.Z. Wang, and H.J. Lin. 2000. Chinese food cooking and lung cancer in women nonsmokers. Am J Epidemiol. 151:140-7. Kotin, P., Falk, H. L., and Busser, R. 1959. Distribution, retention, and elimination of 14C-3,4-benzpyrene after administration to mice and rats. J. Natl. Cancer Inst. 23:541-555. Ling, T.Y., M.D. Kuo, C.L. Li, A.L. Yu, Y.H. Huang, T.J. Wu, Y.C. Lin, S.H. Chen, and J. Yu. 2006. Identification of pulmonary Oct-4+ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro. Proc Natl Acad Sci U S A. 103:9530-5. Linnoila, R.I., E. Szabo, F. DeMayo, H. Witschi, C. Sabourin, and A. Malkinson. 2000. The role of CC10 in pulmonary carcinogenesis: from a marker to tumor suppression. Ann N Y Acad Sci. 923:249-67. Luch, A. 2005. Nature and nurture - lessons from chemical carcinogenesis. Nat Rev Cancer. 5:113-25. MacKenzie, K.M., and D.M. Angevine. 1981. Infertility in mice exposed in utero to benzo(a)pyrene. Biol Reprod. 24:183-91. Meuwissen, R., and A. Berns. 2005. Mouse models for human lung cancer. Genes Dev. 19:643-64. Nakahara, T., K. Hashimoto, M. Hirano, M. Koll, C.R. Martin, and V.R. Preedy. 2003. Acute and chronic effects of alcohol exposure on skeletal muscle c-myc, p53, and Bcl-2 mRNA expression. Am J Physiol Endocrinol Metab. 285:E1273-81. Oreffo, V.I., A. Morgan, and R.J. Richards. 1990. Isolation of Clara cells from the mouse lung. Environ Health Perspect. 85:51-64. Osborne, M.R., R.G. Harvey, and P. Brookes. 1978. The reaction of trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene with DNA involves attack at the N7-position of guanine moieties. Chem Biol Interact. 20:123-30. Panani, A.D., and C. Roussos. 2006. Cytogenetic and molecular aspects of lung cancer. Cancer Lett. 239:1-9. Patel, J.H., A.P. Loboda, M.K. Showe, L.C. Showe, and S.B. McMahon. 2004. Analysis of genomic targets reveals complex functions of MYC. Nat Rev Cancer. 4:562-8. Perez, D.S., R.J. Handa, R.S. Yang, and J.A. Campain. 2008. Gene expression changes associated with altered growth and differentiation in benzo[a]pyrene or arsenic exposed normal human epidermal keratinocytes. J Appl Toxicol. 28:491-508. Reynolds, S.D., K.U. Hong, A. Giangreco, G.W. Mango, C. Guron, Y. Morimoto, and B.R. Stripp. 2000. Conditional clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells. Am J Physiol Lung Cell Mol Physiol. 278:L1256-63. Risch, A., and C. Plass. 2008. Lung cancer epigenetics and genetics. Int J Cancer. 123:1-7. Rom, W.N., J.G. Hay, T.C. Lee, Y. Jiang, and K.M. Tchou-Wong. 2000. Molecular and genetic aspects of lung cancer. Am J Respir Crit Care Med. 161:1355-67. Salamone, M.F. 1981. Toxicity of 41 carcinogens and noncarcinogenic analogs. In: de Serres, F.J. and J. Ashby, Eds. Evaluation of Short-term Tests for Carcinogens. Report of the International Corroborative Program. Progress in Mutation Research. 1:682-685. Sanders, E.J., M. Varedi, and A.S. French. 1993. Cell proliferation in the gastrulating chick embryo: a study using BrdU incorporation and PCNA localization. Development. 118:389-99. Scherer, G., C. Conze, A.R. Tricker, and F. Adlkofer. 1992. Uptake of tobacco smoke constituents on exposure to environmental tobacco smoke (ETS). Clin Investig. 70:352-67. Shimada, T., K. Inoue, Y. Suzuki, T. Kawai, E. Azuma, T. Nakajima, M. Shindo, K. Kurose, A. Sugie, Y. Yamagishi, Y. Fujii-Kuriyama, and M. Hashimoto. 2002. Arylhydrocarbon receptor-dependent induction of liver and lung cytochromes P450 1A1, 1A2, and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in genetically engineered C57BL/6J mice. Carcinogenesis. 23:1199-207. Shimizu, Y., Y. Nakatsuru, M. Ichinose, Y. Takahashi, H. Kume, J. Mimura, Y. Fujii-Kuriyama, and T. Ishikawa. 2000. Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A. 97:779-82. Shinozaki, R., S. Inoue, and K.S. Choi. 1998. Flow cytometric measurement of benzo[a]pyrene-diol-epoxide-DNA adducts in normal human peripheral lymphocytes and cultured human lung cancer cells. Cytometry. 31:300-6. Singh, G., and S.L. Katyal. 2000. Clara cell proteins. Ann N Y Acad Sci. 923:43-58. Sivarajah, K., K.G. Jones, J.R. Fouts, T. Devereux, J.E. Shirley, and T.E. Eling. 1983. Prostaglandin synthetase and cytochrome P-450-dependent metabolism of (+/-)benzo(a)pyrene 7,8-dihydrodiol by enriched populations of rat Clara cells and alveolar type II cells. Cancer Res. 43:2632-6. Sohn, S.H., K.N. Kim, I.K. Kim, E.I. Lee, J.J. Ryu, and M.K. Kim. 2008. Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 23:423-34. Sun, J.D., R.K. Wolff, and G.M. Kanapilly. 1982. Deposition, retention, and biological fate of inhaled benzo(a)pyrene adsorbed onto ultrafine particles and as a pure aerosol. Toxicol Appl Pharmacol. 65:231-44. Swanson, H.I., and J.H. Yang. 1999. Specificity of DNA binding of the c-Myc/Max and ARNT/ARNT dimers at the CACGTG recognition site. Nucleic Acids Res. 27:3205-12. Szabo, E., A. Goheer, H. Witschi, and R.I. Linnoila. 1998. Overexpression of CC10 modifies neoplastic potential in lung cancer cells. Cell Growth Differ. 9:475-85. Thyssen, J., J. Althoff, G. Kimmerle, and U. Mohr. 1981. Inhalation studies with benzo[a]pyrene in Syrian golden hamsters. J Natl Cancer Inst. 66:575-7. Tice, R.R., E. Agurell, D. Anderson, B. Burlinson, A. Hartmann, H. Kobayashi, Y. Miyamae, E. Rojas, J.C. Ryu, and Y.F. Sasaki. 2000. Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen. 35:206-21. Triolo, A.J., G.E. Aponte, and D.L. Herr. 1977. Induction of aryl hydrocarbon hydroxylase and forestomach tumors ben benzo(a)pyrene. Cancer Res. 37:3018-21. Ueng, T.H., C.C. Hung, M.L. Kuo, P.K. Chan, S.H. Hu, P.C. Yang, and L.W. Chang. 2005. Induction of fibroblast growth factor-9 and interleukin-1alpha gene expression by motorcycle exhaust particulate extracts and benzo(a)pyrene in human lung adenocarcinoma cells. Toxicol Sci. 87:483-96. Vaziri, C., and D.V. Faller. 1997. A benzo[a]pyrene-induced cell cycle checkpoint resulting in p53-independent G1 arrest in 3T3 fibroblasts. J Biol Chem. 272:2762-9. Wang, A., J. Gu, K. Judson-Kremer, K.L. Powell, H. Mistry, P. Simhambhatla, C.M. Aldaz, S. Gaddis, and M.C. MacLeod. 2003. Response of human mammary epithelial cells to DNA damage induced by BPDE: involvement of novel regulatory pathways. Carcinogenesis. 24:225-34. Wattenberg, L.W., and J.L. Leong. 1970. Inhibition of the carcinogenic action of benzo(a)pyrene by flavones. Cancer Res. 30:1922-5. Weiss, R.S., P. Leder, and C. Vaziri. 2003. Critical role for mouse Hus1 in an S-phase DNA damage cell cycle checkpoint. Mol Cell Biol. 23:791-803. Weyand, E.H., and D.R. Bevan. 1986. Benzo(a)pyrene disposition and metabolism in rats following intratracheal instillation. Cancer Res. 46:5655-61. Whitlock, J.P., Jr. 1999. Induction of cytochrome P4501A1. Annu Rev Pharmacol Toxicol. 39:103-25. Yang, S.C., S.N. Jenq, Z.C. Kang, and H. Lee. 2000. Identification of benzo[a]pyrene 7,8-diol 9,10-epoxide N2-deoxyguanosine in human lung adenocarcinoma cells exposed to cooking oil fumes from frying fish under domestic conditions. Chem Res Toxicol. 13:1046-50. Yang, Y., Z. Zhang, A.B. Mukherjee, and R.I. Linnoila. 2004. Increased susceptibility of mice lacking Clara cell 10-kDa protein to lung tumorigenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a potent carcinogen in cigarette smoke. J Biol Chem. 279:29336-40. Yao, B., J. Fu, E. Hu, Y. Qi, and Z. Zhou. 2007. The Cdc25A is involved in S-phase checkpoint induced by benzo(a)pyrene. Toxicology. 237:210-7. Yoshino, I., and Y. Maehara. 2007. Impact of smoking status on the biological behavior of lung cancer. Surg Today. 37:725-34. Zhang, J., and K.R. Smith. 1996. Hydrocarbon emissions and health risks from cookstoves in developing countries. J Expo Anal Environ Epidemiol. 6:147-61. Zheng, M., T.S.M. Wan, M. Fang and F. Wang. 1997. Characterization of the non-volatile organic compounds in the aerosols of Hong Kong—identification, abundance and origin Atmospheric Environ. 31:227-237. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42888 | - |
dc.description.abstract | 苯芘benzo(a)pyrene (BaP),為多環芳香烴物質(Ploycyclic Aromatic Hydrocarban, PAHs),主要大量存在於香菸煙狀物、汽機車排放物及食物燒烤物。BaP 於細胞中經過細胞色素P450及epoxide hydrolase代謝活化生成中間產物BaP diolepoxide (BPDE),BPDE攻擊DNA及大分子蛋白生成供價鍵結,而被認為是BaP致突變性的主要途徑。BaP 已被証實於實驗動物為致突變性、致腫瘤及對人體為可能性致癌,國際癌症中心(International Arctic Research Center, IARC)將BaP列為可能的人類致癌物質(group 2A)之等級。而肺臟是呼吸系統面對外來物的第一防線,其中Clara cells位於支氣管束、支氣管與肺泡交接處被視為是肺臟幹源細胞,含豐富細胞色素-450對外來物之代謝行為具重要角色,但也因此成為許多毒物之目標細胞。文獻報導指出當BaP進入生物體後,在肺部Clara cells及Alveolar type II有高含量累積,引發本篇研究目的在於探討當Clara cells在面對BaP這樣一個經代謝後具致癌性的毒物時細胞之相關反應為何。
實驗利用林泰元博士於2006年發表於美國國家科學院院刊,取老鼠肺臟以無血清方式進行原代培養,建立原代培養細胞中包括Clara related stem/progenitor cells以及mesenchymal stroma cells。實驗首先利用免疫細胞染色以及反轉錄聚合酶鏈鎖反應鑑定細胞表現octamer-binding transcription (Oct4)及Clara cell secretion protein (CCSP)蛋白,確定細胞型態與成熟狀態。接著以0.5至50 μM BaP處理原代培養細胞,24小時後發現細胞增生形情。而分析細胞週期分佈發現,BaP的處理造成S期上升。進一步以BrdU以及CCSP染色標記S期細胞和Clara related stem/progenitor cells發現BaP造成的細胞週期S期上升,是發生在Clara related stem/progenitor cells,然而對mesenchymal stroma cells的細胞週期則沒有影響。 BaP是aryl hydrocarbon receptor(AhR)的ligand,當它進入細胞後會與細胞質的AhR結合發生核轉移,進入細胞再與ARNT活化下游基因表現造成細胞增生以及對外來物的代謝活性。實驗利用反轉錄聚合酶鏈鎖反應以及免疫細胞染色發現於BaP處理4小時後發生AhR核轉移,而活化代謝酵素CYP1A1,CYP1B1表現於12,24小時上升2倍。接著利用即時反轉錄聚合酶鏈鎖反應定量發現,c-myc表現量隨BaP處理時間而上升,於24小時增加至3.5倍。c-myc下游分子的影響,包括了cyclin D1表現於BaP處理24小時增加至4.2倍,CDK4蛋白的表現增加至3.5倍。由此推測BaP造成的S期上升是來自c-myc的活化,因此實驗進一步利用siRNA抑制c-myc作用,發現c-myc的抑制有效地減少BaP誘導之S期上升。 而BaP經代謝活化後生成活性中間產物BPDE是致突變性的來源。實驗利用免疫細胞染色可觀察到BPDE-DNA鍵結物的生成,而BaP於原代培養細胞是否造成基因毒性,利用慧星試驗發現BaP處理24小時後與基因毒性的現象相較於陰性對照組具統計意義增加。 由目前實驗發現,BaP的處理造成c-myc活化,進而啟動下游分子造成細胞週期進入S期。同時BaP的作用於原代培養細胞中造成基因毒性。綜合以上結果推測: BaP處理原代培養細胞於Clara related stem/progenitor cell造成細胞週期進入S期可能與c-myc及其下游分子相關,同時伴隨著BaP所造成的基因毒性細胞可能啟動DNA修補機制而使細胞週期有S期停滯情形,實驗未來將針對基因毒性啟動之DNA修補機制進一步探討。最後,BaP是已知的可能人類致癌物質,Clara related stem/progenitor cells 在進行代謝同時,所生成的BPDE造成之基因毒性是否誘導細胞走向癌化則是本實驗未來方向。 | zh_TW |
dc.description.abstract | Benzo(a)pyrene (BaP) belongs to polycyclic aromatic hydrocarbon (PAH) family of environmental carcinogens that are present in tobacco smoke , barbecued food and auto exhaust. BaP require cytochrome P450 and epoxide hydrolase mediated bio-activation for generation of their respective ultimate carcinogenic dio epoxide intermediates, (+)benzo(a)pyrene 7,8-dihydrodiol-9,10-epoxide (BPDE). Covalent interation of BPDE with DNA is believed to be a critical step in BaP-induced tumorigenesis. BaP have been implicated in the etiology of lung cancer. In the lung, BaP was located in ciliated and non-ciliated Clara and alveolar type II cells, resulting in the experimental animals, such as rat, mice, or rabbit. Clara cells play important role in the metabolism of xenobiotic in the lung, because they have abundant cytochrome P450 monooxygenase. In previously studies, Clara related stem/progenitor cells were identified and generated in lung stem/progenitor cell. Although, the potential roles of Clara cells in metabolism of xenobiotic have been proposed, however, the molecular mechanism of BaP metabolically activation in the Clara related stem/progenitor cells still unclear.
In this work, we set a lung stem/progenitor cell including Clara cell related stem/progenitor cells surrounding with mesenchymal stroma cells to examine the BaP-induced cell response. Different concentration of BaP treatments were applied to lung stem/progenitor cells. The MTT assay showed the high concentration of BaP cause cell proliferation in lung stem/progenitor cells. The cell cycle analysis revealed that S phase increased after BaP treatment for 24 hours. By BrdU incorporation experiment showed that BaP exposure was able to promote Clara related stem/progenitor cell entry to S phase. BaP is a ligand of aryl hydrocarbon receptor(AhR), binding leads to nuclear translocation and interaction with its partner protein AhR nuclear translocator (ARNT) will active xenobiotic metabolism and proliferation. By mRNA and immunocytochemistry analysis, BaP exposure caused AhR translocation to nuclei at 4 hours and activated CYP1A1, CYP1B1 expression at 12 and 24 hours. Further, BaP-induced c-myc, cyclin D1 expression up to 3.5 and 4.2 folds by real-time PCR and CDK4 protein level up to 3.5 folds by western blot analysis. Knockdown of c-myc in lung stem/progenitor cells by siRNA transfection, suppressed S phase distribution for BaP treatment. BaP can be metabolized into BPDE, a ultimate of carcinogen attach to DNA cause genotoxicity. From immunocytochemistry of BPDE DNA positive result reveal that BaP probably cause BPDE DNA adduct in Clara related stem/progenitor cells. And using comet assay, BaP has been shown to cause genotoxicity. The current study showed that BaP activates c-myc expression of lung stem/progenitor cell, and through cyclin D1/CDK4 mediated cell cycle entry to S phase. Meanwhile, BaP treatment also induced CYP1A1 expression and genotoxicity in Clara related stem/progenitor cells. Together, these results indicated that BaP presented the potent carcinogen for lung stem/progenitor cells to undergo tumorigenesis processes. And hinted that S phase increased caused from cell cycle progession by BaP-induced c-myc activation and might result in arrested by genotoxity induced repair mechanism. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T01:27:39Z (GMT). No. of bitstreams: 1 ntu-98-R96447004-1.pdf: 2340338 bytes, checksum: 0a95645e27ea7e7bdf0d4cceec158773 (MD5) Previous issue date: 2009 | en |
dc.description.tableofcontents | 圖表目錄---------------------------------------------- II
中文摘要---------------------------------------------- III 英文摘要---------------------------------------------- V 縮寫表------------------------------------------------ VII 第一章 緒論---------------------------------------- 1 第二章 實驗材料與方法-------------------------------- 10 第三章 實驗結果-------------------------------------- 29 第四章 實驗討論-------------------------------------- 35 第五章 參考文獻-------------------------------------- 43 第六章 圖表集---------------------------------------- 49 | |
dc.language.iso | zh-TW | |
dc.title | Benzo(a)pyrene 於肺臟幹源性Clara 細胞造成之細胞反應 | zh_TW |
dc.title | Cellular Responses to Benzo(a)pyrene in Clara Related Stem/Progenitor Cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林泰元(Thai-Yen Ling),郭明良(Min-Liang Kuo),黃彥華(Yen-Hua Huang),曾淑芬(Shun-Fen Tzeng),林國煌(Kuo-Huang Ling) | |
dc.subject.keyword | 苯芘,肺,幹源細胞,c-myc,Clara cell, | zh_TW |
dc.subject.keyword | Benzo(a)pyrene,BaP,lung,Clara cell,stem/progenitor cell,c-myc, | en |
dc.relation.page | 69 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2009-07-23 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 毒理學研究所 | zh_TW |
顯示於系所單位: | 毒理學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-98-1.pdf 目前未授權公開取用 | 2.29 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。