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研究生(外文):Shu-Farn Wan
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(外文):Tsun-Jen Cheng
外文關鍵詞:Ambient particulate matterDNA breakscomet assayPAHs
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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
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
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