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研究生:萬書帆
研究生(外文):Shu-Farn Wan
論文名稱:大氣懸浮微粒對健康大鼠肺部組織DNA損傷研究
論文名稱(外文):Effects of Ambient Particulate Matter on DNA-damage Capacity in Lung Tissue of Healthy SD Rats
指導教授:鄭尊仁鄭尊仁引用關係
指導教授(外文):Tsun-Jen Cheng
口試日期:2016-07-18
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:86
中文關鍵詞:細懸浮微粒粗懸浮微粒DNA損傷彗星分析法多環芳香烴類
外文關鍵詞:Ambient particulate matterDNA breakscomet assayPAHs
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根據臺灣衛生福利部的資料顯示,癌症為國人10大死因之首,而其中肺癌的死亡率一直位居所有癌症死亡率中的第一位。空氣污染物之中的大氣懸浮微粒被認為是急性與慢性肺部疾病的危險因子。流行病學也有研究顯示肺癌的發生與暴露大氣懸浮微粒相關。另外,許多體外細胞實驗證實大氣懸浮微粒會造成細胞內DNA的損傷;然而,大氣懸浮微粒對動物體內DNA損傷的研究仍然不足。因此,本研究的目的為探討健康的雄性SD大鼠在急性暴露不同粒徑的大氣懸浮微粒之後,其體內肺部組織及周邊血液的DNA損傷程度,同時也分析微粒上化學成分與生物效應之間的相關性。
本實驗暴露所用的大氣微粒來自台北市大安區鄰近基隆高架道路的區域,該區域為台北市交通繁忙的地帶,因此採樣的微粒可以代表台北市交通污染區的微粒特性。採樣時間點為2012年的冬季與2013年的夏季,採樣的粒徑分別為小於10微米的粗懸浮微粒以及小於2.5微米的細懸浮微粒。將採集回來的樣本使用99.9%的甲醇進行超音波震盪將微粒萃取下來,再將萃取下來的微粒分成兩部分,皆使用氮氣將甲醇吹乾,得到乾燥的微粒。一部分的微粒用二氯甲烷回溶,使用氣相層析質譜儀進行多環芳香烴類的成分分析;另一部分的微粒則使用磷酸緩衝溶液回溶進行動物實驗的暴露。本實驗所使用的動物為8週大的雄性SD大鼠,暴露方式為急性的氣管灌注,在暴露之後的24小時後將動物進行犧牲,並且採集新鮮的肺組織與周邊血液立即使用彗星分析法進行DNA損傷的分析,此外也採集肺泡灌洗液進行巨噬細胞與嗜中性球的計數,作為肺部組織發炎反應的指標。
本研究的結果顯示兩個季節的細懸浮微粒比起粗懸浮微粒和控制組在肺部組織與周邊血液皆明顯造成較大程度的DNA損傷以及肺部的發炎反應。此外,我們也發現DNA損傷與微粒上的多環芳香烴類有顯著的相關性。
依據本研究的結果可以得出較小粒徑的大氣懸浮微粒在健康的動物體內會造成較嚴重的DNA損傷,而這樣的結果可能與微粒上的多環芳香烴成分有關。
According to the Ministry of Health and Welfare in Taiwan, lung cancer holds the highest mortality rate among all kinds of cancer. However, ambient particulate matter (PM) has been recognized as a significant risk factor for the acute or chronic pulmonary diseases. Epidemiological studies have also shown the associations between PM exposure and the occurrence of lung cancer. Many in vitro toxicological research have proved that PM would induce DNA damage in cells, whereas in vivo studies about DNA damage caused by the exposure of PM are still insufficient. As a result, the aim of this study is to evaluate the extent of DNA breaks in lung tissue and peripheral blood of healthy SD rats after acute exposure to different size fraction of ambient PM.
PM_2.5 and PM_10 were collected from 2012 winter and 2013 summer in Gongguang, a traffic-related area in Taipei. Samples underwent extraction by methanol. Part of the particles were resuspended in PBS (with < 0.01% vol DMSO) for animal studies, and the rest were used for PAHs analysis through GC/MS. 8-week-old Sprague Dawley rats received particles by intratracheal instillation. 24 hours after exposure, lung tissue and peripheral blood were collected to detect DNA breaks by comet assay. Other inflammatory indicators such as the numbers of macrophage and neutrophil in bronchial alveolar lavage fluid (BALF) were also investigated after the sacrifice of the animals.
Results showed that PM_2.5 from winter and summer both caused larger extent of inflammatory responses in lung tissue and DNA breaks in lung tissue and peripheral blood than PM_10 and control group. In addition, we found significantly positive correlation between DNA breakage and PAHs content of PM.
In conclusion, out study indicates that smaller fraction of PM will result in more serious DNA breaks in healthy animals, which might be related to its chemical composition.
中文摘要 i
ABSTRACT v
Chapter 1 Introduction 1
1.1 Research Background 1
1.2 Objectives 4
Chapter 2 Literature Review 5
2.1 Particulate Matter (PM) 5
2.2 Epidemiological studies on PM-related lung cancer 7
2.3 DNA damage and lung cancer 8
2.4 Mechanisms of PM-induced DNA damage 9
2.5 Mechanisms of PAHs-induced DNA damage 10
Chapter 3 Materials and Methods 12
3.1 Study Design 12
3.2 Time schedule 13
3.3 Animals 13
3.4 PM Sampling 14
3.5 PM extraction and resuspension 14
3.6 Intratracheal instillation (I.T.) 15
3.7 Polycyclic Aromatic Hydrocarbons (PAHs) analysis 16
3.7.1 PAHs extraction and analysis 16
3.7.2 PAHs toxic equivalent (TEQ) 17
3.7.3 PAHs source characteristics 19
3.8 Blood & bronchoalvoelar lavage fluid (BALF) collection 20
3.8.1 Peripheral blood collection 20
3.8.2 Bronchoalveolar lavage fluid (BALF) collection 21
3.9 Alkaline Comet assay 21
3.9.1 Peripheral blood sample preparation 22
3.9.2 Lung tissue sample preparation 22
3.9.3 Assay protocol 23
3.9.4 Data analysis 24
3.10 Statistics 25
Chapter 4 Results 26
4.1 Recovery rate of PM 26
4.2 PAHs analysis 26
4.2.1 PAHs concentration & TEQ 26
4.2.2 PAHs sources description 27
4.3 Inflammatory responses in lung 28
4.3.1 2013 summer 28
4.3.2 2012 winter 29
4.3.3 2013 summer and 2012 winter 29
4.4 DNA breaks in lung tissue 30
4.4.1 Tail moment 30
4.4.2 Tail DNA % 32
4.5 DNA breaks in peripheral blood 32
4.5.1 Tail moment 33
4.5.2 Tail DNA % 33
4.6 Correlation between PAHs and biological outcomes 34
4.5.1 PAHs and inflammatory indicators 34
4.5.2 PAHs and DNA damage 35
4.5.3 DNA damage in lung tissue and peripheral blood 36
4.5.4 DNA damage and inflammatory indicators 36
Chapter 5 Discussion 37
5.1 PAHs analysis 38
5.1.1 PAHs concentration and TEQ 38
5.1.2 PAHs sources description 40
5.2 Lung inflammation and ambient particulate matter 41
5.3 DNA damage in lung tissue and peripheral blood 43
Chapter 6 Conclusions and suggestions 49
1.Andersen, Z.J., et al., Chronic obstructive pulmonary disease and long-term exposure to traffic-related air pollution: a cohort study. Am J Respir Crit Care Med, 2011. 183(4): p. 455-61.
2.Bernstein, J.A., et al., Health effects of air pollution. J Allergy Clin Immunol, 2004. 114(5): p. 1116-23.
3.Dockery, D.W., Epidemiologic Evidence of Cardiovascular Effects of Particulate Air Pollution. Environmental Health Perspectives, 2001. 109((supplement4)): p. 483–486.
4.Raaschou-Nielsen, O., et al., Air pollution from traffic and risk for lung cancer in three Danish cohorts. Cancer Epidemiol Biomarkers Prev, 2010. 19(5): p. 1284-91.
5.C. Arden Pope III, R.T.B., Michael J. Thun, Eugenia E. Calle,Daniel Krewski,Kazuhiko Ito, George D. Thurston, Lung Cancer, Cardiopulmonary Mortality, and Long-term Exposure to Fine Particulate Air Pollution. American Medical Association, 2002. 287(9 ): p. 1132-1141.
6.III, A.J.C.a.C.A.P., Lung cancer and Air pollution. Environmental Health Perspectives, 1995. 103(Suppl 8): p. 219-224.
7.Richard W. Atkinson, G.W.F., H. Ross Anderson, Roy M. Harrison, Ben Armstrong, Urban ambient particle metrics and health_ a time-series analysis. Epidemiology, 2010. 21(4): p. 501-511.
8.Stolzel, M., et al., Daily mortality and particulate matter in different size classes in Erfurt, Germany. J Expo Sci Environ Epidemiol, 2007. 17(5): p. 458-67.
9.Brunekreef, B. and B. Forsberg, Epidemiological evidence of effects of coarse airborne particles on health. Eur Respir J, 2005. 26(2): p. 309-18.
10.Host, S., et al., Short-term associations between fine and coarse particles and hospital admissions for cardiorespiratory diseases in six French cities. Occup Environ Med, 2008. 65(8): p. 544-51.
11.Suneeti S. Mane, D.M.P., and Ih-Chang Hsu, Genotoxic Effects of Five Polycyclic Aromatic Hydrocarbons in Human and Rat Mammary Epithelial Cells. Environmental and Molecular Mutagenesis, 1990. 15: p. 78-82.
12.Torben Nielsen, H.E.J., John Chr. Larsenb, Morten Poulsen, City Air Pollution of polycyclic aromatic hydrocarbons and other mutagens_ occurrence, sources and health effects. The Science of the Total Environmental and Molecular Mutagenesis, 1996. 189/190: p. 41-49.
13.Organization, W.H., Air quality guidelines: global update 2005: particulate matter, ozone, nitrogen dioxide, and sulfur dioxide. 2006: World Health Organization.
14.Turpin, B.J. and J.J. Huntzicker, Identification of secondary organic aerosol episodes and quantitation of primary and secondary organic aerosol concentrations during SCAQS. Atmospheric Environment, 1995. 29(23): p. 3527-3544.
15.Mauderly, J.L. and J.C. Chow, Health effects of organic aerosols. Inhalation toxicology, 2008. 20(3): p. 257-288.
16.Ghelfi, E., Air pollution, reactive oxygen species (ROS), and autonomic nervous system interactions modulate cardiac oxidative stress and electrophysiological changes. 2011: INTECH Open Access Publisher.
17.Cohen, A.J., Outdoor Air Pollution and Lung Cancer. Environmental Health Perspectives, 2000. 108(4): p. 743-750.
18.Ole Raaschou-Nielsen, Z.J.A., Martin Hvidberg, Steen Solvang Jensen, Matthias Ketzel, Mette Serensen, Steffen Loft, Kim Overvad, and Anne Tjenneland, Lung Cancer Incidence and Long-Term Exposure to Air Pollution from Traffic. Environ Health Perspect, 2011. 119: p. 860-865.
19.Turner, M.C., et al., Long-term ambient fine particulate matter air pollution and lung cancer in a large cohort of never-smokers. Am J Respir Crit Care Med, 2011. 184(12): p. 1374-81.
20.Raaschou-Nielsen, O., et al., Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE). The Lancet Oncology, 2013. 14(9): p. 813-822.
21.Hoeijmakers, J.H.J., Genome maintenance mechanisms for preventing cancer. NATURE, 2001. 411: p. 366-374.
22.Elledge, B.-B.S.Z.a.S.J., The DNA damage response_ putting checkpoints in perspective. Nature, 2000. 408: p. 433-439.
23.Kryston, T.B., et al., Role of oxidative stress and DNA damage in human carcinogenesis. Mutat Res, 2011. 711(1-2): p. 193-201.
24.Knaapen, A.M., et al., Neutrophils and respiratory tract DNA damage and mutagenesis: a review. Mutagenesis, 2006. 21(4): p. 225-36.
25.Schins, R.P., Mechanisms of genotoxicity of particles and fibers. Inhal Toxicol, 2002. 14(1): p. 57-78.
26.Knaapen, A.M., et al., Inhaled particles and lung cancer. Part A: Mechanisms. Int J Cancer, 2004. 109(6): p. 799-809.
27.Paul J.A. BORM, R.P.F.S.a.C.A., INHALED PARTICLES AND LUNG CANCER, PART B_ PARADIGMS AND RISKASSESSMENT. Int. J. Cancer, 2004. 110: p. 3-14.
28.Greim, H., et al., Toxicity of fibers and particles. Report of the workshop held in Munich, Germany, 26-27 October 2000. Inhal Toxicol, 2001. 13(9): p. 737-54.
29.Li, N., et al., Ultrafine Particulate Pollutants Induce Oxidative Stress and Mitochondrial Damage. Environmental Health Perspectives, 2002. 111(4): p. 455-460.
30.GIUSEPPE L. SQUADRITO, R.C., BARRY DELLINGER, and WILLIAM A. PRYOR, Quinoid redox cycling as a mechanism for sustained free radical generation by inhaled airborne particulate matter. Free Radical Biology & Medicine, 2001. 31(9): p. 1132-1138.
31.Kenneth Donaldson, D.M.B., Colin Mitchell, Miglena Dineva, Paul H. Beswick, Peter Gilmour, and William MacNee, Free Radical Activity of PM10_ Iron-mediated Generation of Hydroxyl Radicals. Environmental Health Perspectives, 1997. 105(5): p. 1285-1289.
32.Albrecht, C., et al., The crucial role of particle surface reactivity in respirable quartz-induced reactive oxygen/nitrogen species formation and APE/Ref-1 induction in rat lung. Respir Res, 2005. 6: p. 129.
33.IARC, Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures. IARC Monographs on the Evaluation of Carcinogenic Risks toHumans, 2010. 92: p. IARC Press.
34.Huberman, E., et al., Identification of mutagenic metabolites of benzo (a) pyrene in mammalian cells. Proceedings of the National Academy of Sciences, 1976. 73(2): p. 607-611.
35.Conney, A.H., Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: GHA Clowes Memorial Lecture. Cancer research, 1982. 42(12): p. 4875-4917.
36.Harvey, R.G., Polycyclic aromatic hydrocarbons: chemistry and carcinogenicity. 1991: CUP Archive.
37.Baird, W.M. and S.L. Ralston, Carcinogenic polycyclic aromatic hydrocarbons. Comprehensive toxicology, 1997. 12: p. 171-200.
38.Dipple, A., R.C. Moschel, and C.A.H. Bigger, Polynuclear aromatic carcinogens. Chemical carcinogens, 1984. 1: p. 41-163.
39.Levin, W., et al., Evidence that benzo (a) anthracene 3, 4-diol-1, 2-epoxide is an ultimate carcinogen on mouse skin. Cancer research, 1978. 38(6): p. 1705-1710.
40.Nordqvist, M., et al., Metabolism of chrysene and phenanthrene to bay-region diol epoxides by rat liver enzymes. Molecular pharmacology, 1981. 19(1): p. 168-178.
41.Cavalieri, E. and E.G. Rogan, Central role of radical cations in metabolic activation of polycyclic aromatic hydrocarbons. Xenobiotica, 1995. 25(7): p. 677-688.
42.Klinedinst, D.K. and N.R. Drinkwater, Mutagenesis by apurinic sites in normal and ataxia telangiectasia human lymphoblastoid cells. Molecular carcinogenesis, 1992. 6(1): p. 32-42.
43.Bolton, J.L., et al., Role of quinoids in estrogen carcinogenesis. Chemical research in toxicology, 1998. 11(10): p. 1113-1127.
44.Bolton, J.L., et al., Role of quinones in toxicology. Chemical research in toxicology, 2000. 13(3): p. 135-160.
45.Penning, T.M., et al., Dihydrodiol dehydrogenases and polycyclic aromatic hydrocarbon activation: generation of reactive and redox active o-quinones. Chemical research in toxicology, 1999. 12(1): p. 1-18.
46.McCoull, K.D., et al., Synthesis and characterization of polycyclic aromatic hydrocarbon o-quinone depurinating N7-guanine adducts. Chemical research in toxicology, 1999. 12(3): p. 237-246.
47.Shou, M., R.G. Harvey, and T.M. Penning, Reactivity of benzo [a] pyrene-7, 8-dione with DNA. Evidence for the formation of deoxyguanosine adducts. Carcinogenesis, 1993. 14(3): p. 475-482.
48.LAGOY, I.C.T.N.A.P.K., Toxic equivalency factors (TEFs) for polycyclic aromatic hydrocarbons (PAHs) REGULATORY TOXICOLOGY AND PHARMACOLOGY
1992. 16: p. 290-300.
49.Mark B. Yunkera, R.W.M., Roxanne Vingarzanc, Reginald and D.G. H. Mitchelld, Stephanie Sylvestrec, PAHs in the Fraser River basin: a critical appraisal of PAH ratios as indicators of PAH source and compisition. Organic Geochemistry, 2002. 33: p. 489–515.
50.NIELSEN, T., Traffic Contribution of Polycyclic Aromatic Hydrocarbons in the Center of a Large City. Atmospheric Environment, 1996. 30(20): p. 3481-3490.
51.Oliveira, C., et al., Size distribution of polycyclic aromatic hydrocarbons in a roadway tunnel in Lisbon, Portugal. Chemosphere, 2011. 83(11): p. 1588-96.
52.Tobiszewski, M. and J. Namiesnik, PAH diagnostic ratios for the identification of pollution emission sources. Environ Pollut, 2012. 162: p. 110-9.
53.Gehui Wang, S.N., Caie Liu, Liansheng Wang, Identification of dicarboxylic acids and aldehydes of PM10 and PM2.5 aerosols in Nanjing, China. Atmospheric Environment, 2002. 36: p. 1941–1950.
54.Khaiwal Ravindra, A.K.M.a.R.V.G., Health Risk Assessment of Urban Suspended Particulate Matter with Special Reference to Polycyclic Aromatic Hydrocarbons_ A Review. REVIEW ON ENVIRONMENTAL HEALTH, 2001. 16: p. 169-189.
55.de Kok, T.M., et al., Genotoxicity and physicochemical characteristics of traffic-related ambient particulate matter. Environ Mol Mutagen, 2005. 46(2): p. 71-80.
56.Mustafa Odabasia, N.V., Aysun Sofuoglub, Yucel Tasdemirc,Thomas M. Holsenb,, Polycyclic aromatic hydrocarbons (PAHs) in Chicago air. The Science of the Total Environment, 1999. 227: p. 57-67.
57.Whei-May Grace Lee, L.-Y.T., The partitioning model of polycyclic aromatic hydrocarbon between gasous and particulate (PM 10μ) phases in urban atmosphere with high humidity. The Science of the Total Environment, 1994. 145: p. 163-171.
58.Fang, G.C., et al., Characteristic of polycyclic aromatic hydrocarbon concentrations and source identification for fine and coarse particulates at Taichung Harbor near Taiwan Strait during 2004-2005. Sci Total Environ, 2006. 366(2-3): p. 729-38.
59.Fang, G.C., et al., Characteristic study of polycyclic aromatic hydrocarbons for fine and coarse particulates at Pastureland near Industrial Park sampling site of central Taiwan. Chemosphere, 2005. 60(3): p. 427-33.
60.Duan, J., et al., Seasonal variation on size distribution and concentration of PAHs in Guangzhou city, China. Chemosphere, 2007. 67(3): p. 614-22.
61.Hong, H., et al., Seasonal variation of PM10-bound PAHs in the atmosphere of Xiamen, China. Atmospheric Research, 2007. 85(3-4): p. 429-441.
62.Jalava, P.I., et al., Associations of urban air particulate composition with inflammatory and cytotoxic responses in RAW 246.7 cell line. Inhal Toxicol, 2009. 21(12): p. 994-1006.
63.Samuelsen, M., U.C. Nygaard, and M. Lovik, Particle size determines activation of the innate immune system in the lung. Scand J Immunol, 2009. 69(5): p. 421-8.
64.Kanami Orihara, N.D., Vidyanand Anaparti and Redwan Moqbel, What''s new in asthma pathophysiology and immunopathology. Expert Rev. Resp. Med., 2010. 4(5): p. 605-629.
65.Schroder, K., et al., Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol, 2004. 75(2): p. 163-89.
66.Miyata, R. and S.F. van Eeden, The innate and adaptive immune response induced by alveolar macrophages exposed to ambient particulate matter. Toxicol Appl Pharmacol, 2011. 257(2): p. 209-26.
67.Barnes, P.J. and A. Bush, Biology and Assessment of Airway Inflammation. 2012: p. 75-88.
68.Francesca Dominici, R.D.P., Michelle L. Bell, Luu Pham, Aidan McDermott, Scott L. Zeger, Jonathan M. Samet, Fine Particulate Air Pollution and Hospital Admission for Cardiovascular and Respiratory Diseases. American Medical Association, 2006. 295(10).
69.Belleudi, V., et al., Impact of Fine and Ultrafine Particles on Emergency Hospital Admissions for Cardiac and Respiratory Diseases. Epidemiology, 2010. 21(3): p. 414-423.
70.Neas, J.S.a.L.M., Fine Particles Are More Strongly Associated Than Coarse Particles with Acute Respiratory. Epidemiology, 2000. 11(1): p. 6-10.
71.Jin-Hyuk Choi, J.-S.K., Young-Chul Kim, Myung-Haing Cho, Yoon-Shin Kim, Nam-Hyun Chung, Comparative study of PM2.5 - and PM10- induced oxidative stress in rat lung epithelial cells. Journal of Veterinary Science, 2004. 5(1): p. 11-18.
72.de Kok, T.M., et al., Toxicological assessment of ambient and traffic-related particulate matter: a review of recent studies. Mutat Res, 2006. 613(2-3): p. 103-22.
73.Kelly, F.J. and J.C. Fussell, Size, source and chemical composition as determinants of toxicity attributable to ambient particulate matter. Atmospheric Environment, 2012. 60: p. 504-526.
74.Szu-Yuan Liu, T.-J.C., Inhalation Toxicity of Size-Segregated Ambient Particulate Matter in BALB/c Mice. 2014.
75.Happo, M.S., et al., Seasonal variation in chemical composition of size-segregated urban air particles and the inflammatory activity in the mouse lung. Inhal Toxicol, 2010. 22(1): p. 17-32.
76.Becker, S., et al., Seasonal Variations in Air Pollution Particle-Induced Inflammatory Mediator Release and Oxidative Stress. Environmental Health Perspectives, 2005. 113(8): p. 1032-1038.
77.Barry Dellinger, W.A.P., Rafael Cueto, Giuseppe L. Squadrito, Vijay Hegde and Walter A. Deutsch, Role of Free Radicals in the Toxicity of Airborne Fine Particulate Matter. Chem. Res. Toxicol., 2001. 14: p. 1371-1377.
78.Torben Nielsen , A.F., Mona-Lise Binderup, 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. & PoUut. Res., 1999. 6(3): p. 133-137.
79.Xiansi Zhaoa, Z., Gang Chen, Huigang Zhu, and J.Y. Shunhui Jiang Genotoxic activity of extractable organic matter from urban airborne particles in Shanghai, China. Mutation Research, 2002. 514: p. 177-192.
80.Cyrys, J., et al., Elemental composition and sources of fine and ultrafine ambient particles in Erfurt, Germany. Science of The Total Environment, 2003. 305(1-3): p. 143-156.
81.Yuan, F. and Y. Ma, The induction of four different heavy metals detected by micronucleus test of dicaryon lymphocyte. Chin J Public Health, 1999. 15(6): p. 467.
82.Ad M. Knaapen, T.S., Paul J.A. Borm and Roel P.F. Schins, Soluble metals as well as the insoluble particle fraction are involved in cellular DNA damage induced by particulate matter. Molecular and Cellular Biochemistry, 2002. 234/235: p. 317-326.
83.Upadhyay, D., et al., Particulate matter induces alveolar epithelial cell DNA damage and apoptosis: role of free radicals and the mitochondria. Am J Respir Cell Mol Biol, 2003. 29(2): p. 180-7.
84.Annamaria Buschini, F.C., Elena Anceschi, Luca Pasini, Paola Poli, Carlo Rossi, Urban airborne particulate_genotoxicity evaluation of different size fractions by mutagenesis tests on microorganisms and comet assay. Chemoshere, 2001. 44: p. 1723-1736.
85.Hsiao, W.L.W., et al., Cytotoxicity of PM2.5 and PM2.5-10 ambient air pollutants assessed by the MTT and the Comet assays. Mutation Research-Genetic Toxicology and Environmental Mutagenesis, 2000. 471(1-2): p. 45-55.
86.T Shi, A.M.K., J Begerow, W Birmili,PJA Borm,RPF Schins, Temporal variation of hydroxyl radical generation and 8-hydroxyguanosine formation by coarse and fine particulate matter. Occup Environ Med, 2003. 60: p. 315-321.
87.LEONA L. GREENWELL, T.M., TIMOTHY P. JONES,1 and ROY J. RICHARDS, Particle-induced oxidative damage is ameliorated by pulmonary antioxidants. Free Radical Biology & Medicine, 2002. 32(9): p. 898-905.
88.Bonetta, S., et al., DNA damage in A549 cells exposed to different extracts of PM(2.5) from industrial, urban and highway sites. Chemosphere, 2009. 77(7): p. 1030-4.
89.15–20Meng, Z. and Q. Zhang, Damage effects of dust storm PM2.5 on DNA in alveolar macrophages and lung cells of rats. Food Chem Toxicol, 2007. 45(8): p. 1368-74.
90.LIN., Z.-Q., et al., Oxidative Damage to Lung Tissue and Peripheral Blood in Endotracheal PM2.5-treated Rats. BIOMEDICAL AND ENVIRONMENTAL SCIENCES, 2009. 22: p. 223-228.
91.Zhang, W., et al., Pulmonary toxicity study in rats with PM10 and PM2.5: Differential responses related to scale and composition. Atmospheric Environment, 2011. 45(4): p. 1034-1041.
92.Zhang, L., et al., The role of human aldo-keto reductases in the metabolic activation and detoxication of polycyclic aromatic hydrocarbons: interconversion of PAH catechols and PAH o-quinones. Frontiers in pharmacology, 2012. 3: p. 193.
93.Park, J.-H., et al., Evidence for the aldo-keto reductase pathway of polycyclic aromatic trans-dihydrodiol activation in human lung A549 cells. Proceedings of the National Academy of Sciences, 2008. 105(19): p. 6846-6851.
94.Park, J.-H., et al., Formation of 8-oxo-7, 8-dihydro-2''-deoxyguanosine (8-oxo-dGuo) by PAH o-quinones: involvement of reactive oxygen species and copper (II)/copper (I) redox cycling. Chemical research in toxicology, 2005. 18(6): p. 1026-1037.
95.Park, J.-H., et al., Polycyclic aromatic hydrocarbon (PAH) o-quinones produced by the aldo-keto-reductases (AKRs) generate abasic sites, oxidized pyrimidines, and 8-oxo-dGuo via reactive oxygen species. Chemical research in toxicology, 2006. 19(5): p. 719-728.
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