臺灣博碩士論文加值系統

飲食中維生素C及維生素E是否能減緩自由基對DNA氧化性傷害之影響曾反覆被研究。然而過往研究大多以健康成人為主，對於高暴露者的研究相當有限。已知空氣污染暴露會增加體內自由基的產生，而過去研究指出空氣污染與死亡率、疾病率的增加有密切關係。飲食與血液之抗氧化營養素的效能並不一致，而抗氧化營養素攝取情形對於改善與空氣污染物暴露有關之DNA氧化性傷害的作用亦尚未釐清，故本研究利用橫斷性研究設計，以暴露於機動車輛廢氣收費員為對象，評估其飲食維生素C、E及血液中抗氧化力，探討DNA氧化性傷害與飲食維生素C、E及血液中抗氧化力之相關。
本研究對象為120位高速公路收費員，以其尿液中之8-OHdG為生物性指標。暴露評估則以累積PM2.5濃度、飲食維生素C、E及血液抗氧化營養素抗氧化力為指標。
結果顯示，飲食維生素C、E分別與血液水溶性、脂溶性抗氧化力呈顯著正相關(r=0.42, p<0.001; r=0.27, p<0.001)。飲食維生素C、E以及血液水溶性、脂溶性營養素抗氧化力均與尿液8-OHdG濃度呈負相關，其中飲食維生素E與8-OHdG濃度間並達統計上顯著相關(r=-0.23, p<0.05)。而PM2.5暴露量及年齡、BMI則與尿液8-OHdG濃度呈正相關，年齡並與尿液8-OHdG濃度達統計上顯著相關(r=0.23, p<0.05)。飲食及血液中抗氧化營養素濃度只有在第三分位攝取量有保護的作用，但均未達統計上顯著意義。本研究發現，在不包含維生素補充劑的狀態下，維生素C及維生素E均具有降低DNA氧化性傷害的作用，此發現希望可提供高速公路收費員對其DNA氧化性傷害發生之預防的參考依據。

Most studies on diminishing DNA oxidative damages by antioxidant supplementation, such as vitamin C and vitamin E were limited to healthy adult subjects. And the information on high pollutant exposure subjects remains limited. Air pollutant was knowen to generate free radicals, given that, studies have explored the relationship between air pollution and mortality. Moreover, inconsistent results were found between the associations of the anti-oxidative effect with dietary antioxidants and with plasma biomarker. The aim of this cross-sectional study was to evaluate the effects of dietary and plasma antioxidants, in relation to oxidative DNA damage, in the highway toll station workers.
We recruited 120 highway toll station workers as study subjects and using urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) concentration as the DNA damage biomarker. PM2.5, dietary vitamin C and vitamin E, and plasma antioxidant capacity were the markers of exposures.
Dietary vitamin C and vitamin E were found significantly correlated with plasma water-soluble and fat-soluble antioxidant capacities respectively (r=0.42, p<0.001; r=0.27, p<0.001). Dietary vitamin C and vitamin E, and plasma antioxidant capacities were negatively correlated with urinary 8-OHdG level. Dietary vitamin E was significantly correlated with urinary 8-OHdG (r=-0.23, p<0.05). PM2.5, age and BMI were positively correlated with urinary 8-OHdG, whereas age was significantly correlated with urinary 8-OHdG (r=0.23, p<0.05). The protective effect on DNA damage of dietary vitamin C and vitamin E, and plasma antioxidant capacities were only on the third tertile intake, but the odd ratios did not reach the statistical significance.
The results of this study suggest that, even without the vitamins supplementation, dietary vitamin C and vitamin E could be protective to DNA damages. This may offer certain guideline for improving health and prevention on DNA damages for highway toll station workers.

目 錄
正文目錄 3
表目錄 5
附錄 6
中文摘要 7
英文摘要 9


正文目錄
第一章 前言 11
第一節 研究背景 11
第二節 研究目的 14
第二章 文獻探討 15
第一節 懸浮微粒特性與成分相關研究 15
第二節 多環芳香烴化合物 17
第三節 氧化壓力與致癌機轉之介紹 18
第四節 氧化營養素維生素C與維生素E簡介 19
第五節 氧化壓力指標-8-HYDROXYDEOXYGUANOSINE (8-OHDG) 23
第三章 研究架構與研究假設 27
第一節 研究架構 27
第二節 研究假設 28
第四章 研究方法與步驟 29
第一節 研究對象 29
第二節 研究地理位置 29
第三節 研究工具 30
第四節 資料收集方法與步驟 30
第五節 懸浮微粒空氣採樣--間接暴露評估 33
第六節 尿中8-OHDG分析 34
第七節 抗氧化力分析方法 36
第八節 實驗室品質管制 37
第九節 統計分析方法 39

第五章 結果 43
第一節 研究對象描述性檢定 43
第二節 抗氧化營養素、PM2.5與8-OHDG描述及檢定 46
第三節 影響8-OHDG相關變項之描述與檢定 48
第六章 討論 55
第一節 8-OHDG濃度 55
第二節 抗氧化營養素-維生素C及維生素E 57
第三節 研究限制 59
第七章 結論 60
參考文獻 62


表 目 錄
表1 問卷之信效度 68
表2 研究對象依性別之基本人口學資料描述與檢定 69
表3 研究對象依性別之生活習慣描述 71
表4 研究對象依性別之研究對象飲食、抗氧化力與暴露相關變項描述與檢定 73
表5 影響8-OHdG濃度相關變項描述與檢定 74
表6 研究對象飲食、抗氧化力與暴露Spearman等級相關係數 76
表7 PM2.5暴露量三分位與8-OHdG濃度相關變項之分佈與共變數分析 77
表8 以羅吉斯迴歸分析log8-OHdG與影響因子的關係 79
表9 血液抗氧化力影響尿中8-OHdG濃度之迴歸模式 81
表10. 飲食維生素影響尿中8-OHdG濃度之迴歸模式 82
表11. 不含補充劑使用之維生素C、E攝取與高log8-OHdG濃度危險性之羅吉斯迴歸分析 83

附 錄
附錄一 84
附錄二 101
附錄三 103
附錄四 104
附錄五 105
附錄六 106
附錄七 107

參考文獻
Alfaro-Moreno, E., Martinez, L., Garcia-Cuellar, C., Bonner, J. C., Murray, J. C., Rosas, I., et al. (2002). Biologic effects induced in vitro by pm10 from three different zones of mexico city. Environ Health Perspect, 110, 715-720.
Aoshiba, K., Koinuma, M., Yokohori, N. and Nagai, A. (2003). Immunohistochemical evaluation of oxidative stress in murine lungs after cigarette smoke exposure. Inhal Toxicol, 15, 1029-1038.
Autrup, H., Daneshvar, B., Dragsted, L. O., Gamborg, M., Hansen, M., Loft, S., Okkels, H., Nielsen, F., Nielsen, P. S., Raffn, E., Wallin, H. and Knudsen, L. E. (1999). Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress. Environ Health Perspect, 107, 233-238.
Block, G., Dietrich, M., Norkus, E. P., Morrow, J. D., Hudes, H., Caan, B. and Packer, L. (2002). Factors associated with oxidative stress in human populations. Am J Epidemiol 156, 274-285.
Bolton, J. L., et al. (2000). Role of quinones in toxicology. Chemical research toxicology, 13, 136-160.
Borja-Aburto, V. H., Castillejos, M., Gold, D. R., Bierzwinski, S., and Loomis, D. (1998). Mortality and ambient fine particles in southwest mexico city, 1993-1995. Environ Health Perspect, 106, 849-855.
Bruner, S. D., Norman, D. P., Fromme, J. C. and Verdine, G. L. (2000). Structural and mechanistic studies on repair of 8-oxoguanine in mammalian cells. Cold Spring Harb Symp Quant Biol, 65, 103-111.
Bruno, R. S., Ramakrishnan, R., Montine, T. J., Bray, T. M. and Traber, M. G. (2002).α-Tocopherol disappearance is faster in cigarette smokers and is inversely related to their ascorbic acid ststus. Am J Clin Nutr 81, 95-103.
Casillas, A. M., Hiura, T., Li, N., and Nel, A. E. (1999). Enhancement of allergic inflammation by diesel exhaust particles: Permissive role of reactive oxygen species. Ann Allergy Asthma Immunol, 83, 624-629.
Castillejos, M., et al. (2000). Airborne coarse particles and mortality. Inhalation Toxicology, 12, 61-72.
Cheng, K. C., Cahill, D. S., Kasai, H., Nishimura, S. and Loeb, L. A. (1992). 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G----T and A----C substitutions. J Biol Chem, 267, 166-172.
Chiou, C. C., Chang, P. Y., Chan, E. C., Wu, T. L., Tsao, K. C. and Wu, J. T. (2003). Urinary 8-hydroxydeoxyguanosine and its analogs as DNA marker of oxidative stress: development of an ELISA and measurement in both bladder and prostate cancers. Clin Chim Acta, 334, 87-94.
Chow, C. K. (1991). Vitamin E and oxidative stress. Free Rad Biol Med 11, 215-232.
Chuang, C. Y., Lee, C. C., Chang, Y. K. and Sung, F. C. (2003). Oxidative DNA damage estimated by urinary 8-hydroxydeoxyguanosine: influence of taxi driving, smoking and areca chewing. Chemosphere, 52, 1163-1171.
Cooke, M. S., Evans, M. D., Herbert, K. E. and Lunec, J. (2000). Urinary 8-oxo-2'-deoxyguanosine--source, significance and supplements. Free Radic Res, 32, 381-397.
de Zwart, L. L., Meerman, J. H., Commandeur, J. N.andVermeulen, N. P. (1999). Biomarkers of free radical damage applications in experimental animals and in humans. Free Radic Biol Med, 26, 202-226.
Dockery, D. W. (2001). Epidemiologic evidence of cardiovascular effects of particulate air pollution. Environ Health Perspect, 109 Suppl 4, 483-486.
Dockery, D. W., Pope, C. A., 3rd, Xu, X., Spengler, J. D., Ware, J. H., Fay, M. E., Ferris, B. G., Jr.and Speizer, F. E. (1993). An association between air pollution and mortality in six U.S. cities. N Engl J Med, 329, 1753-1759.
Finlayson-Pitts, B. J. and Pitts, J. N. Jr. (1997). Tropospheric air pollution: ozone, airborne toxics, polycyclic aromatic hydrocarbons, and particles. Science 276, 1045-1052.
Holman, C. (1999). Source of air pollution. In S. J. Holgate ST (Ed.), Air pollution and health (pp. 115-148). London.
Huang, H. Y., Helzlsouer, K. J. and Appel, L. J. (2000). The effect of vitamin C and vitamin E on oxidative DNA damage: results from a randomized controlled trial. Cancer Epidemiol, Biomarkers& Prevention 9, 647-652.
Jacob, R. A., Aiello, G. M., Stephensen, C. B., Blumberg, J. B., Milbury, P. E., Wallock, L. M. and Ames, B. N. (2003). Moderate antioxidant supplementation has no effect on biomarkers of oxidant damage in healthy men with low fruit and vegetable intakes. J Nutr 133, 740-743.
Kallner, A., Hartmann, D. and Hornig, D. (1979). Steady-state turnover and and body
pool of ascorbic acid in man. Am J Clin Nutr 32, 530-539.
Kelly, F. J. (2003). Oxidative stress: its role in air pollution and adverse health effects. Occup Environ Med, 60, 612-616.
Krishna G., Urda G. and Theiss J. (1998). Principles and practices of integrating genotoxicity evaluation into routine toxicology studies: a pharmaceutical industry perspective. Environmental & Molecular Mutagenesis. 32, 115-120.
Kristenson, M., Kucinskiene, Z., Schafer-Elinder, L., Leanderson, P. and Tagesson, C. (2003). Lower serum levels of β-carotene in Lithuanian men are accompanied by higher urinary excretion of the oxidative DNA adduct, 8-hydroxydeoxyguanosine: the LiVicordia study. Nutrition 19, 11-15.
Lagorio, S. e. a. (1994). Exposure to benzene and urinary concentrations of 8-hydroxydeoxyguanosine, a biological marker of oxidative damage to DNA. occuptl and environ medicine, 51, 739-743.
Lenton, K. J., Therriault, H., Cantin, A. M., Fülöp, T., Payette, H. and Wagner, J. R. (2000). Direct correlation of glutathione and ascorbate and their dependence on age and season in human lymphocytes. Am J Clin Nutr 71, 1194-1120.
Lai, C. H., Lin, H. C., Shih, T. S., Chen J. S., Tsai, J. S., Yang, T., Jaakkola J. J. K. and Strickland, P. T. (2005). Exposure to traffic exhausts and oxidative DNA damage. Occup Environ Med 62, 216-222.
Lai C. H., Liou S. H., Shih T. S., Tsai P. J., Chen H. L., Chang Y. C., Buckley T. J., Strickland P. T. and Jaakkola J. J. K. (2004). Exposure to fine particulate matter (PM2.5) among highway toll station workers in Taipei: direct and indirect exposure assessment. Archives of Environmental Health. 59, 138-48.
Li, N., Hao, M., Phalen, R. F., Hinds, W. C., & Nel, A. E. (2003). Particulate air pollutants and asthma. A paradigm for the role of oxidative stress in pm-induced adverse health effects. Clin Immunol, 109, 250-265.
Liu, L., Zhang, Q., Feng, J., Deng, L., Zeng, N., Yang, A. and Zhang, W. (1996). The study of DNA oxidative damage in benzene-exposed workers. Muta Res 370, 145-150.
Loft, S. and Poulsen, H. E. (1996). Cancer risk and oxidative DNA damage in man. J Mol Med, 74, 297-312.
Loft, S., Vistisen, K., Ewertz, M., Tjonneland, A., Overvad, K.andPoulsen, H. E. (1992). Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender and body mass index. Carcinogenesis, 13, 2241-2247.
Lutsenko, E. A., Carcamo, J. M. and Golde, D. W. (2002). Vitamin C prevents DNA mutation induced by oxidative stress. J Biol Chem 277, 16895-16899.
Marangon, K., Herbeth, B., Lecomte, E., Paul-Dauphin, A., Grolier, P., Chancerelle, Y., Artur, Y. and Siest, G. (1998). Diet, antioxidant status, and smoking habits in French men. Am J Clin Nutr 67, 231-239.
Mayne, S. T. (2003). Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative stress status in epidemiologic research. J Nutr 133, 933S-940S.
Mǿller, P., Vogel, U., Pedersen, A., Dragsted, L. O., Sandström, B. and Loft, S. (2003). No effect of 600 gram fruit and vegetables per day on oxidative DNA damage and repair in healthy nonsmokers. Cancer Epidemiol, Biomarkers& Prevention 12, 1016-1022.
Nel, A. E., Diaz-Sanchez, D., and Li, N. (2001). The role of particulate pollutants in pulmonary inflammation and asthma: Evidence for the involvement of organic chemicals and oxidative stress. Curr Opin Pulm Med, 7, 20-26.
Nightingale, J. A., Maggs, R., Cullinan, P., Donnelly, L. E., Rogers, D. F., Kinnersley, R., et al. (2000). Airway inflammation after controlled exposure to diesel exhaust particulates. Am J Respir Crit Care Med 162, 161-16
Osornio-Vargas, A. R., Bonner, J. C., Alfaro-Moreno, E., Martinez, L., Garcia-Cuellar, C., Ponce-de-Leon Rosales, S., et al. (2003). Proinflammatory and cytotoxic effects of mexico city air pollution particulate matter in vitro are dependent on particle size and composition. Environ Health Perspect 111, 1289-1293.
Popov, I. and Lewin, G. (1994). Photochemiluminescent detection of antiradical activity. Ⅱ. Testing of non-enzymic water-soluble antioxidants. Free Rad Biol Med 17, 267-271.
Popov, I. and Lewin, G. (1996). Photochemiluminescent detection of antiradical activity. Ⅳ. Testing of lipid-soluble antioxidants. J Biochem Biophys Methods 31, 1-8
Radak, Z., Pucsuk, J., Boros, S., Josfai, L.andTaylor, A. W. (2000). Changes in urine 8-hydroxydeoxyguanosine levels of super-marathon runners during a four-day race period. Life Sci, 66, 1763-1767.
Rozalski, R., Gackowski, D., Roszkowski, K., Foksinski, M. and Olinski, R. (2002). The level of 8-hydroxyguanine, a possible repair product of oxidative DNA damage, is higher in urine of cancer patients than in control subjects. Cancer Epidemiol Biomarkers Prev, 11, 1072-1075.
Ruef, J., Moser, M., Kubler, W. and Bode, C. (2001). Induction of endothelin-1 expression by oxidative stress in vascular smooth muscle cells. Cardiovasc Pathol 10, 311-315.
Schwartz, J., Norris, G., Larson, T., Sheppard, L., Claiborne, C., & Koenig, J. (1999). Episodes of high coarse particle concentrations are not associated with increased mortality. Environ Health Perspect 107, 339-342.
Sǿrensen, M., Autrup, H., Hertel, O., Wallin, H., Knudsen, L. F. and Loft , S. (2003). Personal exposure to PM2.5 and biomarkers of DNA damage. Cancer Epidemiol, Biomarkers& Prevention 12, 191-196.
Tagesson, C., Kallberg, M., Klintenberg, C.and Starkhammar, H. (1995). Determination of urinary 8-hydroxydeoxyguanosine by automated coupled-column high performance liquid chromatography: a powerful technique for assaying in vivo oxidative DNA damage in cancer patients. Eur J Cancer, 31A, 934-940.
Takeuchi, T. and Morimoto, K. (1993). Increased formation of 8-hydroxydeoxyguanosine, an oxidative DNA damage, in lymphoblasts from Fanconi's anemia patients due to possible catalase deficiency. Carcinogenesis, 14, 1115-1120.

Wefers, H. and Sies, H. (1998). The protection by ascorbate and glutathione against microsomal lipid peroxidation is dependent on vitamin E. Eur J Biochem 174, 353-357.
Yatsuzuka, M., Tazawa, K., Yasuda, T., Yoshii, M., Ogawa, K.and Wada, S. (2004). Identification of hydroxyl radicals after UV irradiation of aqueous extracts of cigarette smoke and evaluation of urinary 8-OHdG in smokers. Asian Pac J Cancer Prev, 5, 279-283.
Zhang, J., Ichiba, M., Hanaoka, T., Pan, G., Yamano, Y., Hara, K., Takahashi, K.and Tomokuni, K. (2003). Leukocyte 8-hydroxydeoxyguanosine and aromatic DNA adduct in coke-oven workers with polycyclic aromatic hydrocarbon exposure. Int Arch Occup Environ Health, 76, 499-504.
呂鋒洲(1995) 環境毒物引起的自由基。自由基生物學與醫學3，29-35。
蔡坤志(2002) 自由基簡介與其臨床應用。臨床醫學49，123-129。
丁克祥、姚鳳祥、邊慶華、許鳳山、何寶嬋、高青花、吳永沃、張愛玲、陳華東和屠瑋武(1995) 自由基致癌、促癌作用及其發生機制。自由基生物學與醫學3，57-61。
行政院衛生署. (2004). 衛生食品衛生處. from http://www.doh.gov.tw/cht/list.aspx?dept=R&now_fod_list_no=4225&class_no=3&level_no=1&divNo=3&divCount=5
行政院衛生署. (2005). 食品資訊網. from http://food.doh.gov.tw/chinese/health/health_5.htm
陳秀瑩、陳曉華、傅偉光. (2002). 台灣地區食品營養成分資料庫（二）:食品工業發展研究所.
吳彩邑. (2005). 葉酸與乳癌關係之病例對照研究: 國防醫學院公共衛生研究所碩士論文.
古琇瑩. (2005). 機動車輛廢氣暴露對氧化壓力及基因毒性影響之研究: 國防醫學院公共衛生研究所碩士論文.