請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/5505
標題: 台灣中部地區空氣懸浮微粒之水溶性及脂溶性萃取物誘發人類乳癌細胞之細胞毒性和DNA氧化損害
Induction of cytotoxic response and oxidative DNA damage in human breast cancer cell lines by water- and solvent-extractable particulate matter in central Taiwan
作者: 劉懿賢
Liu, Yi-Shian
關鍵字: Particulate matter
懸浮微粒
Oxidative stress
Gene expression
氧化壓力
基因表現
出版社: 環境工程學系所
引用: Aristizabal B., Cobo M., Hoyos A., Montes de Correa C., Abalos M., Martinez K., Abad E., and Rivera J., 2008, Baseline levels of dioxin and furan emissions from waste thermal treatment in Colombia. Chemosphere. Bai, N., Khazaei, M., van Eeden, S.F. et al. 2007. The Pharmacology of Particulate Matter Air Pollution-Induced Cardiovascular Dysfunction. Pharmacol. Ther. , 113, 16-29. Bai, Y., Suzuki, A.K., Sagai, M. 2001. The Cytotoxic Effects of Diesel Exhaust Particles on Human Pulmonary Artery Endothelial Cells in Vitro: Role of Active Oxygen Species. Free Radic. Biol. Med. , 30, 555-562. Bayer-Oglesby, L., Schindler, C., Hazenkamp-von Arx, M.E. et al. 2006. Living Near Main Streets and Respiratory Symptoms in Adults: The Swiss Cohort Study on Air Pollution and Lung Diseases in Adults. Am. J. Epidemiol. , 164, 1190-1198. Binkova, B., Cerna, M., Pastorkova, A. et al. 2003. Biological Activities of Organic Compounds Adsorbed Onto Ambient Air Particles: Comparison between the Cities of Teplice and Prague during the Summer and Winter Seasons 2000-2001. Mutat. Res. , 525, 43-59. Bonner, M.R., Han, D., Nie, J. et al. 2005. Breast cancer risk and exposure in early life to polycyclic aromatic hydrocarbons using total suspended particulates as a proxy measure. Cancer Epidemiol Biomarkers Prev. , 14(1), 53-60 Brits, E., Schoeters, G., Verschaeve, L. 2004. Genotoxicity of PM10 and Extracted Organics Collected in an Industrial, Urban and Rural Area in Flanders, Belgium. Environ. Res. , 96, 109-118. Bronzetti, G., Cini, M., Paoli, M. et al. 1997. Mutagenicity and Chemical Analysis of Airborne Particulate Matter Collected in Pisa. J. Environ. Pathol. Toxicol. Oncol. , 16, 147-156. Brown, R.K., Wyatt, H., Price, J.F. et al. 1996. Pulmonary Dysfunction in Cystic Fibrosis is Associated with Oxidative Stress. Eur. Respir. J. , 9, 334-339. Buschini, A., Cassoni, F., Anceschi, E. et al. 2001. Urban Airborne Particulate: Genotoxicity Evaluation of Different Size Fractions by Mutagenesis Tests on Microorganisms and Comet Assay. Chemosphere , 44, 1723-1736. Calderon-Garciduenas, L., Franco-Lira, M., Torres-Jardon, R. et al. 2007. Pediatric Respiratory and Systemic Effects of Chronic Air Pollution Exposure: Nose, Lung, Heart, and Brain Pathology. Toxicol. Pathol. , 35, 154-162. Chang L. P., Tsai J. H., Chang K. L. and Lin J. J., 2008, Water-soluble inorganic ions in airborne particulates from the nano to coarse mode: a case study of aerosol episodes in southern region of Taiwan. Environ Geochem Health. 30, 291–303 Cheng M. T., Tsai Y. I., and Chang W. C., 2000, Chemical Compositions and Size Distribution of Water Soluble Aerosols Collected in Central Taiwan, Proceedings of the Australia-Taiwan Joint Symposium on Environment Modeling and Management, Taichung, Taiwan, June 28-30, p.20-26. Chen, K.S., Lin, C.F., Chou, Y.M. 2001. Determination of Source Contributions to Ambient PM2.5 in Kaohsiung, Taiwan, using a Receptor Model. J. Air Waste Manag. Assoc. , 51, 489-498. Chiaverini, L. 2002. Asthma, Particulates, and Diesel Exhaust. Med. Health R. I. , 85, 140-142. Courter, L.A., Musafia-Jeknic, T., Fischer, K. et al. 2007. Urban Dust Particulate Matter Alters PAH-Induced Carcinogenesis by Inhibition of CYP1A1 and CYP1B1. Toxicol. Sci. , 95, 63-73. Dagher, Z., Garcon, G., Gosset, P. et al. 2005. Pro-Inflammatory Effects of Dunkerque City Air Pollution Particulate Matter 2.5 in Human Epithelial Lung Cells (L132) in Culture. J. Appl. Toxicol. , 25, 166-175. de Kok, T.M., Driece, H.A., Hogervorst, J.G. et al. 2006. Toxicological Assessment of Ambient and Traffic-Related Particulate Matter: A Review of Recent Studies. Mutat. Res. , 613, 103-122. de Kok, T.M., Hogervorst, J.G., Briede, J.J. et al. 2005. Genotoxicity and Physicochemical Characteristics of Traffic-Related Ambient Particulate Matter. Environ. Mol. Mutagen. , 46, 71-80. Delgado-Rodriguez, A., Ortiz-Marttelo, R., Villalobos-Pietrini, R. et al. 1999. Genotoxicity of Organic Extracts of Airborne Particles in Somatic Cells of Drosophila Melanogaster. Chemosphere , 39, 33-43. Dellinger, B., Pryor, W.A., Cueto, R. et al. 2001. Role of Free Radicals in the Toxicity of Airborne Fine Particulate Matter. Chem. Res. Toxicol. , 14, 1371-1377. Dockery, D.W., Pope, C.A.,3rd, Xu, X. et al. 1993. An Association between Air Pollution and Mortality in Six U.S. Cities. N. Engl. J. Med. , 329, 1753-1759. Don Porto Carero, A., Hoet, P.H., Verschaeve, L. et al. 2001. Genotoxic Effects of Carbon Black Particles, Diesel Exhaust Particles, and Urban Air Particulates and their Extracts on a Human Alveolar Epithelial Cell Line (A549) and a Human Monocytic Cell Line (THP-1). Environ. Mol. Mutagen. , 37, 155-163. Donaldson, K., Brown, D.M., Mitchell, C. et al. 1997. Free Radical Activity of PM10: Iron-Mediated Generation of Hydroxyl Radicals. Environ. Health Perspect. , 105 Suppl 5, 1285-1289. Ducatti, A., Vargas, V.M. 2003. Mutagenic Activity of Airborne Particulate Matter as an Indicative Measure of Atmospheric Pollution. Mutat. Res. , 540, 67-77. Fang, G.C., Chang, K.F., Lu, C. et al. 2004. Estimation of PAHs Dry Deposition and BaP Toxic Equivalency Factors (TEFs) Study at Urban, Industry Park and Rural Sampling Sites in Central Taiwan, Taichung. Chemosphere , 55, 787-796. Fang, G.C., Wu, Y.S., Chang, C.N. et al. 2006. A Study of Polycyclic Aromatic Hydrocarbons Concentrations and Source Identifications by Methods of Diagnostic Ratio and Principal Component Analysis at Taichung Chemical Harbor Near Taiwan Strait. Chemosphere , 64, 1233-1242. Fang, G.C., Chang, K.F., Lu, C. and Bai, H. 2004. Estimation of PAHs dry deposition and BaP toxic equivalency factors (TEFs) study at Urban, Industry Park and rural sampling sites in central Taiwan, Taichung. Chemosphere, 55:787-796. Farmer, P.B., Singh, R., Kaur, B. et al. 2003. Molecular Epidemiology Studies of Carcinogenic Environmental Pollutants. Effects of Polycyclic Aromatic Hydrocarbons (PAHs) in Environmental Pollution on Exogenous and Oxidative DNA Damage. Mutat. Res. , 544, 397-402. Fubini, B., Hubbard, A. 2003. Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) Generation by Silica in Inflammation and Fibrosis. Free Radic. Biol. Med. , 34, 1507-1516. Gabelova, A., Valovicova, Z., Horvathova, E. et al. 2004. Genotoxicity of Environmental Air Pollution in Three European Cities: Prague, Kosice and Sofia. Mutat. Res. , 563, 49-59. Gilli, G., Pignata, C., Schiliro, T. et al. 2007. The Mutagenic Hazards of Environmental PM2.5 in Turin. Environ. Res. , 103, 168-175. Gilmour, P.S., Brown, D.M., Lindsay, T.G. et al. 1996. Adverse Health Effects of PM10 Particles: Involvement of Iron in Generation of Hydroxyl Radical. Occup. Environ. Med. , 53, 817-822. Greenwell, L.L., Moreno, T., Jones, T.P. et al. 2002. Particle-Induced Oxidative Damage is Ameliorated by Pulmonary Antioxidants. Free Radic. Biol. Med. , 32, 898-905. Gutierrez-Castillo, M.E., Roubicek, D.A., Cebrian-Garcia, M.E. et al. 2006. Effect of Chemical Composition on the Induction of DNA Damage by Urban Airborne Particulate Matter. Environ. Mol. Mutagen. , 47, 199-211. Healey, K., Lingard, J.J., Tomlin, A.S. et al. 2005. Genotoxicity of Size-Fractionated Samples of Urban Particulate Matter. Environ. Mol. Mutagen. , 45, 380-387. Hetland, R.B., Cassee, F.R., Refsnes, M. et al. 2004. Release of Inflammatory Cytokines, Cell Toxicity and Apoptosis in Epithelial Lung Cells After Exposure to Ambient Air Particles of Different Size Fractions. Toxicol. In. Vitro. , 18, 203-212. Ho, W.C., Hartley, W.R., Myers, L. et al. 2007. Air Pollution, Weather, and Associated Risk Factors Related to Asthma Prevalence and Attack Rate. Environ. Res. Hsiao, W.L., Mo, Z.Y., Fang, M. et al. 2000. Cytotoxicity of PM(2.5) and PM(2.5--10) Ambient Air Pollutants Assessed by the MTT and the Comet Assays. Mutat. Res. , 471, 45-55. Hukkanen, J., Lassila, A., Paivarinta, K. et al. 2000. Induction and Regulation of Xenobiotic-Metabolizing Cytochrome P450s in the Human A549 Lung Adenocarcinoma Cell Line. Am. J. Respir. Cell Mol. Biol. , 22, 360-366. Karlsson, H.L., Ljungman, A.G., Lindbom, J. et al. 2006. Comparison of Genotoxic and Inflammatory Effects of Particles Generated by Wood Combustion, a Road Simulator and Collected from Street and Subway. Toxicol. Lett. , 165, 203-211. Karlsson, H.L., Nygren, J., Moller, L. 2004. Genotoxicity of Airborne Particulate Matter: The Role of Cell-Particle Interaction and of Substances with Adduct-Forming and Oxidizing Capacity. Mutat. Res. , 565, 1-10. Kato, M., Nakano, M., Morikawa, A., Kimura, H., Shigeta, M., Kuroume, T. 1991. Ability of polymorphonuclear leukocytes to generate active oxygen species in children with bronchial asthma. Use of chemiluminescence probes with a Cypridina luciferin analog and luminal. Int. Arch. Allergy Appl. Immunol. 95, 17– 22. Khillare P. S., Tripti Agarwal, and Vijay Shridhar, 2008, Impact of CNG implementation on PAHs concentration in the ambient air of Delhi: A comparative assessment of pre- and post-CNG scenario. Environ Monit Assess. Knaapen, A.M., Shi, T., Borm, P.J. et al. 2002. Soluble Metals as Well as the Insoluble Particle Fraction are Involved in Cellular DNA Damage Induced by Particulate Matter. Mol. Cell. Biochem. , 234-235, 317-326. Krewski, D., Rainham, D. 2007. Ambient Air Pollution and Population Health: Overview. J. Toxicol. Environ. Health A , 70, 275-283. Kuo, C.Y., Hsu, Y.W., Lee, H.S. 2003. Study of Human Exposure to Particulate PAHs using Personal Air Samplers. Arch. Environ. Contam. Toxicol. , 44, 454-459. Li, C.S. and Ro, Y.S. 2000. Indoor characteristics of polycyclic aromatic hydrocarbons in the urban atmosphere of Taipei. Atom. Environ., 34, 611-620. Li, N., Kim, S., Wang, M., Froines, J., Sioutas, C., Nel, A. 2002. Use of a stratified oxidative stress model to study the biological effects of ambient concentrated and diesel exhaust particulate matter. Inhal. Toxicol. 14, 459–486. Li, N., Sioutas, C., Cho, A. et al. 2003. Ultrafine Particulate Pollutants Induce Oxidative Stress and Mitochondrial Damage. Environ. Health Perspect. , 111, 455-460. Lin, T.C., Chang, F.H., Hsieh, J.H. et al. 2002. Characteristics of Polycyclic Aromatic Hydrocarbons and Total Suspended Particulate in Indoor and Outdoor Atmosphere of a Taiwanese Temple. J. Hazard. Mater. , 95, 1-12. Massolo, L., Muller, A., Tueros, M. et al. 2002. Assessment of Mutagenicity and Toxicity of Different-Size Fractions of Air Particulates from La Plata, Argentina, and Leipzig, Germany. Environ. Toxicol. , 17, 219-231. Mates, J.M., Perez-Gomez, C., Blanca, M. 2000. Chemical and Biological Activity of Free Radical ''Scavengers'' in Allergic Diseases. Clin. Chim. Acta , 296, 1-15. Matsumoto, H., Adachi, S., Suzuki, Y. 2005. Bisphenol A in Ambient Air Particulates Responsible for the Proliferation of MCF-7 Human Breast Cancer Cells and its Concentration Changes Over 6 Months. Arch. Environ. Contam. Toxicol. , 48, 459-466. Meng, Z., Zhang, Q. 2007. Damage Effects of Dust Storm PM(2.5) on DNA in Alveolar Macrophages and Lung Cells of Rats. Food Chem. Toxicol. Muller, A., Alzuet, P., Herbarth, O. et al. 2001. Assessment of Toxicity and Mutagenicity in Air Particulate Matter from an Urban Industrial Area in the Coast of the Rio De La Plata. Environ. Toxicol. , 16, 151-157. Nielsen, T., Feilberg, A., Binderup, M.L. 1999. The variation of street air levels of PAH and other mutagenic PAC in relation to regulations of traffic emissions and the impact of atmospheric processes. Environ. Sci. Pollut. Res. 6, 133–137. Palmgren, F., Wahlin, P., Loft, S. 2003. The Pollution of Air with Particles in Copenhagen. Ministry of the Environment, Copenhagen, (in Danish). Pohjola, S.K., Lappi, M., Honkanen, M. et al. 2003. Comparison of Mutagenicity and Calf Thymus DNA Adducts Formed by the Particulate and Semivolatile Fractions of Vehicle Exhausts. Environ. Mol. Mutagen. , 42, 26-36. Pozzi, R., Berardis, B.D., Paoletti, L.,and Guastadisegni, C. 2003. Inflammatory mediators induced by coarse (PM 2.5-10) and fine (PM 2.5) urban air particles in RAW 264.7 cells. Toxicology 183, 243-254. Prahalad, A.K., Inmon, J., Dailey, L.A. et al. 2001. Air Pollution Particles Mediated Oxidative DNA Base Damage in a Cell Free System and in Human Airway Epithelial Cells in Relation to Particulate Metal Content and Bioreactivity. Chem. Res. Toxicol. , 14, 879-887. Šišović A., Bešlić I., Šega K., and Vadjić V., 2008, PAH mass concentrations measured in PM10 particle fraction. Environment International. Samet, J.M., Dominici, F., Curriero, F.C. et al. 2000. Fine Particulate Air Pollution and Mortality in 20 U.S. Cities, 1987-1994. N. Engl. J. Med. , 343, 1742-1749. Shaheen, N. Shah, Munir H., and Jaffar, M., 2005, A study of airborne selected metals and particle size distribution in relation to climatic variables and their source identification. Water, air and soil pollution, p275-294 Sharma A. K., Jensen K. A., Rank J., White P. A., Lundstedt S., Gagne R., Jacobsen N. R., Kristiansen J., Vogel U., and Wallin H., 2007, Genotoxicity, inflammation and physico-chemical properties of fine particle samples from an incineration energy plant and urban air. Mutation Research 633. 95–111 Shi, T., Knaapen, A.M., Begerow, J. et al. 2003. Temporal Variation of Hydroxyl Radical Generation and 8-Hydroxy-2''-Deoxyguanosine Formation by Coarse and Fine Particulate Matter. Occup. Environ. Med. , 60, 315-321. Sorensen, M., Autrup, H., Moller, P. et al. 2003. Linking Exposure to Environmental Pollutants with Biological Effects. Mutat. Res. , 544, 255-271. Rison, L., Møller, P., and Loft, S., 2005, Oxidative stress-induced DNA damage by particulate air pollution , Mutation Research 592 , p119–137. Tong, Y., Ni, X., Zhang, Y. et al. 2002. Study of the Toxicological Mechanism of Acidified Aerosols. Biol. Trace Elem. Res. , 85, 149-156. Upadhyay, D., Panduri, V., Ghio, A. et al. 2003. Particulate Matter Induces Alveolar Epithelial Cell DNA Damage and Apoptosis: Role of Free Radicals and the Mitochondria. Am. J. Respir. Cell Mol. Biol. , 29, 180-187. Wilson M. R., Foucaud L., Barlow P. G., Hutchison G. R., Sales J., Simpson R. J., Stone V., 2007, Nanoparticle interactions with zinc and iron: Implications for toxicology and inflammation. Toxicology and Applied Pharmacology 225, 80–89 Valavanidis, A., Vlahoyianni, T., Fiotakis, K. 2005. Comparative Study of the Formation of Oxidative Damage Marker 8-Hydroxy-2''-Deoxyguanosine (8-OHdG) Adduct from the Nucleoside 2''-Deoxyguanosine by Transition Metals and Suspensions of Particulate Matter in Relation to Metal Content and Redox Reactivity. Free Radic. Res. , 39, 1071-1081. Vallyathan V., Pack D., and Leonard S., 2007, Journal of Toxicology and Environmental Health, Part A, 70: 95–106. Vineis, P., Husgafvel-Pursiainen, K. 2005. Air Pollution and Cancer: Biomarker Studies in Human Populations. Carcinogenesis , 26, 1846-1855. Zhao, X., Wan, Z., Chen, G. et al. 2002. Genotoxic Activity of Extractable Organic Matter from Urban Airborne Particles in Shanghai, China. Mutat. Res. , 514, 177-192. Zhao, X.H., Wang, X.L., Li, X.Y. 2001. Automobile Exhaust Particle-Induced Apoptosis and Necrosis in MRC-5 Cells. Toxicol. Lett. , 122, 103-110. 莊秉潔(2006),台灣火力電廠環境空氣品質平行監測期末報告 莊惠萍(2005),屏東地區空氣污染對易感性族群健康影響之研究,高雄醫學大學公共衛生學研究所碩士論文 何燕婷,中臺灣長期觀測亞洲沙塵暴的研究,2007,國立中興大學環境工程學系碩士論文 柳中明、楊之遠,2002,影響台灣空氣品質的大陸沙塵天氣:2002年個案研究。中華民國環境保護學會學刊第25卷第2期,153-177 張順欽,亞洲沙塵暴對空氣品質影響與測報,2002,中華民國環境保護學會學刊第25卷第2期,134-152 郭育良等人(2005),職業病概論,華杏出版股份有限公司 黃俊智(2000),焚化爐衍生空氣污染物特性分析之研究,國立屏東科技大學環境工程與科學系碩士學位論文 黃群真(2006),戴奧辛誘發人類乳癌細胞株(MCF-7及MDA-MB-231 cells)細胞毒性及核酸氧化損壞作用研究,國立中興大學環境工程學研究所碩士論文 林家琦(2007),懸浮微粒脂溶性萃取物誘發人類乳癌細胞及肺纖維母之毒性和DNA損害,國立中興大學環境工程學研究所碩士論文 蔡尚學(2003),台灣地區室外空氣污染對健康效應之研究,高雄醫學大學醫學研究所博士論文 謝振友(1999),台北市垃圾焚化爐排氣對周界懸浮微粒之影響評估,國立臺灣大學環境工程學研究所碩士論文 雷侑蓁(2005),空氣懸浮微粒心肺毒性研究,國立台灣大學職業醫學與工業衛生研究所博士論文
摘要: 空氣懸浮微粒是具有健康危害效應的物質。文獻指出,空氣懸浮微粒上所吸附的脂溶性、水溶性及其他物質,是造成細胞胞內氧化壓力累積生成的重要因素之一。此外文獻亦提到,氧化壓力會造成人體老化、內分泌失調以及癌症等疾病。因此探討空氣懸浮微粒形成氧化壓力以及細胞毒性的機制,可以協助了解空氣懸浮微粒致細胞毒性及致癌作用機轉。本研究目的主要是去探討,曝露在空氣懸浮微粒之水溶性萃取樣本下,細胞內部是否為經由代謝活化效應誘發基因表現失衡,進而造成細胞胞內氧化壓力、DNA損害以及細胞死亡。本研究利用多種生物性指標,包括細胞存活率測試(SRB assay)、氧化壓力測定法(Fluorescence assay)、DNA單股斷裂分析法(COMET assay)以及西方墨點法(Western blot),針對懸浮微粒可能產生之細胞毒性、氧化壓力、基因損害以及基因表現進行研究與分析。根據實驗結果顯示,曝露在空氣懸浮微粒水溶性萃取物質下,不論是MDA-MB-231細胞還是MCF-7細胞均無明顯的細胞毒性效應生成。研究結果也顯示出,曝露於空氣懸浮微粒水溶性萃取物2小時下即有氧化壓力顯著上升。在懸浮微粒誘發DNA單股損害部分,三個採樣點的水溶性萃取液均能造成兩種乳癌細胞顯著之DNA單股斷裂。此外針對細胞之基因表現部分,MCF-7細胞曝露在東大以及草屯採樣站脂溶性樣本萃取物下,其p53蛋白有明顯上升;曝露於三個採樣站之脂溶性樣本則會造成CYP1A1代謝酵素明顯增加。綜合本研究之結果可知,空氣懸浮微粒的水溶性萃取物質,可以造成人類乳癌細胞胞內氧化壓力上升及基因單股斷裂。而脂溶性萃取物質則會造成MCF-7細胞p53以及CYP1A1基因大量表現,進而造成細胞凋亡以及胞內氧化壓力之生成。
URI: http://hdl.handle.net/11455/5505
其他識別: U0005-2508200814241100
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