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研究生:胡韶婷
研究生(外文):Shao-Ting Hu
論文名稱:香椿水萃取物之基因毒性評估
論文名稱(外文):Genotoxicity of water extracts from Toona sinensis Roemor leaf
指導教授:鍾雲琴
指導教授(外文):Yun-Chin Chung
學位類別:碩士
校院名稱:靜宜大學
系所名稱:食品營養研究所
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2007/07/
畢業學年度:95
語文別:中文
論文頁數:87
中文關鍵詞:香椿水萃取物基因毒性評估
外文關鍵詞:GenotoxicityToona sinensis Roemor leaf
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本研究目的為以ICR(Hauschka Ha/ICR)小鼠探討香椿葉水萃物(water extract of Toona sinensis leaf;TSL-1)的安全性。TSL-1的致突變性利用安姆試驗(Ames test)評估, 結果顯示於測試劑量範圍內TSL-1對所有的測試菌株(Salmonella typhimurium TA98、TA100、TA102及TA1535)皆無致突變性。在90天亞慢性毒性試驗中,給予ICR雄鼠與雌鼠(各10隻)TSL-1 (1000 mg /kg BW)連續90天,於90天試驗期間,並無任何實驗動物死亡或有任何不良反應。進一步對實驗動物進行血清生化值分析及臟器病理切片,所有結果與控制組(未餵食TSL-1)比較並無明顯差異。亞慢性毒性試驗中所評估之各項變因,並未顯示長期餵食TSL-1會造成明顯之差異,此結果證實TSL-1並不會蓄積毒性。此外,本研究亦測定TSL-1對老鼠週邊血液多染色質紅血球微核(micronucleated polychromatic erythrocytes ;MNPEC)發生率及以多染色質紅血球數目與單染色質數目(polychromatic erythrocytes/normochromatic erythrocytes;PEC/NEC)之比值作為細胞毒性指標。分別餵食3.8、7.5、15mg/kg BW之TSL-1之小鼠與控制組比較,無論公鼠或母鼠其MNPEC及PEC/NEC index值與控制組無顯著差異。因此,TSL-1之無毒性劑量(the no-observed-adverse-effect-level ,NOAEL)應高於1000 mg/kg bw/day。
關鍵字: 香椿、安姆試驗、亞慢性口服毒性、無毒性劑量、微核試驗、週邊血液多染色質紅血球微核發生率、單染色質紅血球微核發生率、多染色質紅血球數目與單染色質數目比值。
The purposes of this study were to evaluate the safety of water extracts from Toona sinensis Roemor leaf (TSL-1) using ICR mice as the animal model. The mutagenic properties of TSL-1 was investigated using Ames test, and no mutagenicity was found toward all tester strains (Salmonella typhimurium TA98, TA100, TA102 and TA1535). In the subchronic toxicity study, an oral daily dose of 1000 mg TSL-1/kg BW was given to male and female ICR mice. No mortality or adverse effect was observed during a 90-day period. Compared with untreated mice, all treated ICR mice not only maintained alive, but did not show substantial side effect. Furthermore, macroscopic appearance and histopathological examination of the target organs were found to be normal. The results of subacute toxicity study indicated the absence of cumulative toxicity of TSL-1, as reflected by the insignificant alterations in the investigated parameters. Micronuleus test indicated that TSL-1, in a single dose of 3.8, 7.5 or 15mg/kg BW, did not alter the quantity of micronucleated polychromatic erythrocytes (MNPCE) and micronucleated normochromatic erythrocytes (MNNCE) and the ratio of polychromatic erythrocytes to normochromatic erythrocytes (PEC/NEC) on the ICR mice. Thus the no-observed-adverse-effect-level (NOAEL) of TSL-1 was greater than 1000 mg/kg bw/day.
Keywords: Toona sinensis Roemor;Ames test;subchronic toxicity study;Micronuleus test ;no-observed-adverse-effect-level (NOAEL)
Abstract 4
摘要 6
前言 8
第一章文獻回顧 10
第一節 香椿簡介 10
一、成份分析 12
二、胺基酸種類 15
三、 微量元素之含量 15
四、 維生素種類 15
五、 生理功能 15
第二節 毒性試驗之項目 29
一、基因毒性試驗(Genotoxicty study) 29
二、基因毒性測試方法 31
第三節 微生物基因突變試驗(Ames test) 33
一、 測試菌株之特性 34
二、 其他突變代表意義 34
三、 Rat liver post-mitochondrial fraction 37
四、 試驗方法 37
五、 結果判定標準 38
第四節 染色體異常分析 40
一、 染色體變異(chromosomal aberration) 40
二、姊妹染色分體交換(sister chromatid exchange) 41
三、微核測試(micronucleus test) 41
第五節 重覆劑量毒性試驗 44
一、急性毒性試驗(Acute toxicity study) 44
二、28天亞急性毒性試驗 45
三、90天亞慢性毒性試驗(90-day feeding toxicity study) 46
四、180天慢性毒性試驗 48
第二章 材料與方法 49
第一節 致突變性之評估 49
第二節 亞慢性毒性試驗(90-day feeding toxicity study) 57
第三節囓齒類骨髓細胞之微核測試法(Micronuclei in bone marrow cells of rodents) 60
第三章 結果 62
第一節 致突變分析 62
第二節 亞慢性毒性試驗 63
第三節 囓齒類骨髓細胞之微核試驗 64
第四章 討論 66
參考文獻 77
王珮憓。2001。椿葉水萃取液在Alloxan所誘發的糖尿病鼠中降血糖作用之研究。高雄醫學大學醫學研究所碩士論文。
甘偉松。1980。臺灣藥用植物誌:第1-3卷。中國醫藥研究所出版。
行政院衛生署。1999。健康食品管理法。台北。
吳琇卿。2003。豬苓多糖及併用WR-2721對輻射與化學性遺傳損傷的防護作用研究。中國醫藥學院中國醫學研究所博士論文。
李熙,謝莉莉。2005。香椿葉的研究概。遼寧中醫學院學報7(3):280-281。
林信伶。2004。香椿之保肝、抗病毒、抗癌之藥理活性及細胞內NO/cGMP路徑之調節作用。高雄醫學大學醫學研究所碩士論文。
侯懷恩,盂慶法。1997。香椿老葉的開發利用價值。中國林副特產41(2):17-19。
徐沛甄,徐雯敏,許勝光,廖俊旺,王銘富,詹吟菁。2003。香椿葉萃取物對老化促進小白鼠學習記憶能力之影響。中華民國營養學會第29屆年會暨學術研討會手冊。
徐沛甄,許勝光,王銘富,廖俊旺,詹吟菁。2003。香椿葉萃取物對老化促進小鼠腦部氧化狀態及老化病理變化之影響。台灣農化與食品科學42(3):199-206。
徐雯敏。2004。香椿對老化促進小鼠學習記憶能力、抗氧化狀態與精子品質之影響。靜宜大學食品營養研究所碩士論文。
翁慶豐、張尚麟、羅智緯。2004。香椿水萃取液乾燥粉劑對肝細胞分裂與肝臟傷害時肝臟再生之調節。農業科技計畫執行成果摘要報告頁733-734。
馬加隆。2004。乳酸醱酵對香椿化學及抗氧化性之影響。屏東科技大學碩士論文。
陳文穎、陳彥任、王珮憓、呂勝義、許勝光。2004。椿葉萃取物對血小板凝集的作用。台灣保健食品學會第二屆第二次年會壁報論文。
程劍華、李以鑌。1998。抗癌植物藥及其驗方。江西科學出版社頁608。
黃俞榮。2004。香椿葉萃取液對非小細胞肺癌細胞株之抗癌功能研究。高雄醫學大學醫學研究所碩士論文。
黃純淇。2004。香椿葉水萃取液對HL-60與K-562細胞株氧化性傷害之影響。高雄醫學大學醫學研究所碩士論文。
黃靖容。2005。香椿之抗氧化及抗癌活性之探討。中國醫藥大學碩士論文。
新編中藥大辭典。1985。新文出版公司頁4205-07。
楊玉嬌、王珮憓、魏明治、呂勝義、陳彥任、許勝光。2004。香椿之嗎啡樣鎮痛作用。台灣保健食品學會第二屆第二次年會壁報論文。
楊馥瑜。2003。香椿對人類精子生理功能之探討。國立成功大學碩士論文。
葛多云。2005。香椿葉中胺基酸和營養元素分析。微量元素與健康研究22(6):1-3。
蔡易真。2003。香椿葉水萃取液對BV-2小神經膠細胞株之抗發炎機制。高雄醫學大學醫學研究所碩士論文。
戴光展。2004。發酵對香椿葉中沒食子酸含量及抗氧化性之影響。屏東科技大學碩士論文。
羅曉東,吳少華,馬云保,吳大剛。2001。椿葉的化學成分研究。中草藥32(5):390-391。
Al-Sabti K, Metcalfe CD. 1995. Fish micronuclei for assessing genotoxicity in water. Mutat Res 343:121-35.
Ames BN, Mccann J, Yamasaki E. 1975. Methods for detecting carcinogens and mutagens with Salmonella / Mammalian-microsome mutagenicity test. Mutat Res 31:347-64.
Ames BN, McCann J. 1981. Validation of the Salmonella test: a reply to rinkus and legator. Cancer Res 41(10):4192-6.
Belpaeme K, Delbeke K, Zhu L, Kirsch-Volders M. 1996. Cytogenetic studies of PCB77 on brown trout (Salmo trutta fario) using the micronucleus test and the alkaline comet assay. Mutagenesis 11(5): 485-92.
Bolognesi C, Landini E, Roggieri P, Fabbri R, Viarengo A. 1999. Genotoxicity biomarkers in the assessment of heavy metal effects in mussels: experimental studies. Environ Mol Mutagen 33(4):287–92.
Calomme M, Pieters L, Vlietinck A, Vanden BD. 1996. Inhibition of bacterial mutagenesis by Citrus flavonoids. Planta Med 62: 222-6.
Cariello NF, Piegorsch WW. 1996. The Ames test: the two-fold rule revisited. Mutat Res 369:23-31.
Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB. 1987. Evaluation of a tetrazolium-based semiautomated colorimetric assay. Assessment of chemosensitivity testing. Cancer Res 47(4):936-46.
Chang HC, Hung WC, Huang MS, Hsu HK. 2002. Extract from the leaves of Toona sinensis Roemor exerts potent anti-proliferative effect on human cancer cells. Am J Chin Med 30:307-14
Cheng JYL, Chen CK, Cheng BJ, Cheng MJ, Chang HH, Chen WJ, Hong HHC, Lee CC, Liang PJ, Sheu SC, Sung KS, Weng YY, Tsai CN, Wang CW, Wang CS, Yen MH, Yu LS, Yu JYL. 2004. A guideline for the care and use of laboratory animals. 2nd ed. Taiwan: Chinese Society for the Laboratory Animal Science. p 1-207.
Chia YC. 2005. A study on the isolation of antitumor compound from Toona sinensis Roemor. Report of Health Food Project (in Chinese)
Dacre JC. 1974. Long-term toxicity study of n-propyl gallate in mice. Food Cosmet Toxicol 12(1):125–9.
Eaton DL, Klaassen CD. 2001. Principles of toxicology. In: Klassen CD editors. Casarett & Doull’s Toxicology: The Basic Science of Poisons. 6 th ed. New York: McGraw-Hill Companies Inc. p 11-34.
Edmonds JM, Staniforth M. 1998. Toona sinensis: Meliaceae. Curtis''s Bot Mag 15(3):186-93.
Fenech M., Chang WP, Kirsch-Volders M, Holland N, Bonassi S, Zeiger E. 2003. Detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat Res 534 (1):65-75.
Gali HU, Perchellet EM, Klish DS, Johnson JM, Perchellet JP. 1992. Antitumor-promoting activities of hydrolyzable tannins in mouse skin. Carcinogenesis 13(4):715-8.
Gali HU, Perchellet EM, Perchellet JP. 1991. Inhibition of tumor promoter-induced ornithine decarboxylase activity by tannic acid and other polyphenols in mouse epidermis, in vivo. Cancer Res 51:2820-5.
Glick Z. 1981. Modes of action of gallic acid in suppressing food intake of rats. J Nutr 111:1910-6.
Grisolia CK, Starling FL. 2001. Micronuclei monitoring of fishes from Lake Parano, under influence of sewage treatment plant discharges. Mutat Res 491(1-2):39–44.
Haschek WM, Rousseaux CG, Wallig MA. 2001. Handbook of Toxicologic Pathology. 2nd ed. New York: Academic Press. p 1-1706.
Haschek WM, Rousseaux CG. 1996. Hepatobiliary System. In: Haschek WM, Rousseaux CG, editors. Fundamental of Toxicologic Pathology. 6th ed. New York: Academic Press. p 121-51.
Hasumura M, Yasuhara K, Tamura T, Imai T, Mitsumori K, Hirose M. 2004. Evaluation of the toxicity of enzymatically decomposed rutin with 13-weeks dietary administration to Wistar rats. Food Chem Toxicol 42:439-44.
Hsieh TJ, Chang FR, Wu YC. 1999. The constituents of Cananga odorata. J Chin Chem Soc 46:607-11.
Hsu HK, Yang YC, Hwang JH, Hong SJ. 2003. Effects of Toona sinensis leaf extract on lipolysis in differentiated 3T3-L1 adipocytes. Kaohsiung J Med Sci 19:385-90.
Kirsch-Volders M, Sofuni T, Aardema M, Albertini S, Eastmond D, Fenech M, Ishidate M, Jr., Lorge E, Norppa H, Surralles J, von der Hude W, Wakata A. 2003. Report from the in vitro micronucleus assay working group. Mutat Res 540(2):153–63.
Klobucar GI, Pavlica M, Erben R, Papes D. 2003. Application of the micronucleus and comet assays to mussel Dreissena polymorpha haemocytes for genotoxicity monitoring of freshwater environments. Aquat Toxicol 64(1):15-23.
Liang CT, Chang MH, Hong CC, Huang KJ. 1999. Establishing the blood chemistry reference values for SPF rats and mice. J Chin Med 25: 55-68.
Liao JW, Hsu CK, Wang MF, Hsu WM, Chan, YC. 2006. Beneficial effect of Toona sinensis Roemor on improving the cognitive performance and brain degeneration in senescence accelerated mice. Br J Nutr 96(2):400-7.
Luo XD, Wu SH, Ma YB, Wu DG. 2000. Limonoids and phytol derivatives from Cedrela sinensis. Fitoterapia 71(5):492-6.
Mahon GAT, Green MHL, Middleton B, Mitchell I de G, Robinson WD, Tweats DJ. 1989. Analysis of data from microbial colony assays. In: Kirkland DJ, editor. Statistical evaluation of mutagenidty test data. Cambridge: Cambridge University Press. p 26-65.
Maines MD, Costa G, Reed DJ, Sassa S, Sipes IG. 2000. Current protocols in toxicology. New York: John Wiley & Sons Inc.
Maron DM, Ames BN. 1983. Revised methods for the Salmonella mutagenicity test. Mutat Res 113:173-215.
Morino K, Matsukara N, Kawachi T, Ohgaki H, Sugumura T, Hirono I. 1982. Carcinogenicity test of quercetin and rutin in golden hamsters by oral adminstration. Carcinogenesis 3:93-7.
Mortelmans K, Zeiger E. 2000. The Ames Salmonella/microsome mutagenicity assay. Mutat Res 455:29-60.
Nakagawa Y, Tayama S. 1995. Cytotoxicity of propyl gallate and related compounds in rat hepatocytes. Arch Toxicol 69:204-8.
Nakayama T, Hiramitsu M, Osawa T, Kawakishi S. 1993. The protective role of gallic acid esters in bacterial cytotoxicity and SOS responses induced by hydrogen peroxide. Mutat Res 303:29-34.
Oiano Neto J, Da silva M, Fatima Das GF, Rodrigues FE, Fernandes JB, Vieira PC, Pinheiro AL. 1998. Norlimonoids from seeds of Toona ciliata. Phytochemistry 49:1369-73.
Orten JM, Kuyper AC, Smith AH. 1948. Studies on the toxicity of propyl gallate and of antioxidant mixtures containing propyl gallate. Food Techn 2:308-16.
Park JC, Yu YB, Lee JH, Choi JS, OK KD. 1996. Phenolic compounds from the rachis of Cedrela sinensis. Kor J Pharmacogn 27(3):219-23.
Poon SL, Leu SF, Hsu HK, Liu MY, Huang BM. 2005. Regulatory mechanism of Toona sinensis on mouse leyding cell steroigogensis. Life Sci 76:1473-87.
Rajalakshmi K, Devaraj H, Devaraj SN. 2001. Assessment of the no-observed-adverse-effect level (NOAEL) of gallic acid in mice. Food Chem Toxicol 39:919-22.
Rao GN. 2002. Diet and kidney diseases in rats. Toxicol Patho 30(6):651-6.
Rooney DE, Czepulkowski BH. 1992. Human cytogenetics: A practical approach. 2nd ed. Oxford: IRL Press.
Sakaguchi N, Inoue M, Ogihara Y. 1998. Reactive oxygen species and intracellular Ca2+-common signals for apoptosis induced by gallic acid. Biochem Pharmacol 55:1973-81.
Schmid W. 1975. The micronucleus test. Mutat Res 31: 9-15.
Serrano A, Palacios C, Roy G, Cespon C, Villar ML, Nocito M, Porque PG. 1998. Derivatives of gallic acid induce apoptosis in tumoral cell lines and inhibit lymphocyte proliferation. Arch Biochem Biophys 350:49-54.
Singleton VL. 1981. Naturally occurring food toxicants: phenolic substances of plant origin common in foods. Adv Food Res 27:149-242.
Steel RGD, Torrie JH. 1980. Principles and procedures of statistics: A biometrical approach. 2nd ed. New York: McGraw-Hill Company.
Tsai IL, Jeng YF, Duh CY, Chen IS. 2001. Cytotoxic constituents from the leaves of Litsea akoensis. Chin Pharm J 53(6):291-301.
van der Heijden CA, Janssen PJ, Strik JJ. 1986. Toxicology of gallates: a review and evaluation. Food and Chem Toxicol 24:1067-70.
Wang YW. 2000. DNA Mutation and Repair. [DPhil thesis]. University of National Taiwan University.
Yang RY. 2003. Application of different analytical methods for studies on antioxidant activities of vegetables. In: Thomas Kalb. AVRDC Progress Report. Shanhua, Taiwan: The world vegetable center. p 117-20.
Yang YC, Hsu HK, Hwang JH, Hong SJ. 2003. Enhancement of glucose uptake in 3T3-L1 adipocytes by Toona sinensis leaf extract. Kaohsiung J Med Sci 19:327-33.
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