Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/15401
標題: 國產基因改造木瓜之基因毒理和動物毒理安全性評估
studies on genetic and feeding toxicities of genetically modified papaya fruit
作者: 林怡絹
Lin, Yi-Juan
關鍵字: genetically modified;基因改造木瓜;papaya genotoxicity;feeding toxicity;基因毒理;動物毒理
出版社: 獸醫病理生物學研究所
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摘要: 
木瓜含有豐富的營養及維生素,為台灣重要栽培的果樹。然而,台灣木瓜產業受木瓜輪點病毒(papaya ringspot virus; PRSV)危害甚鉅,造成嚴重經濟損失。有鑑於此,中興大學葉錫東教授研發基因改造木瓜作為防治對策,選殖PRSV鞘蛋白基因至木瓜,使其對PRSV具有高度抗病能力。因基因改造木瓜的食用安全性仍有許多爭議,故本論文擬探討抗PRSV基因改造木瓜之基因毒理及動物毒理試驗結果,作為食用安全性評估之參考依據。本試驗樣品為台農2號木瓜母本作物及抗PRSV木瓜16-0-1及18-2-4之生果及熟果,經冷凍乾燥所得之凍乾粉末共6種。依照我國衛生署訂出的基因改造食品安全性評估方法,分別評估基因毒理試驗與動物毒性試驗。基因毒性試驗分為體內(in vivo)與體外(in vitro)測試,包括對沙門氏菌回復突變致變異性之Ames試驗、中國倉鼠卵巢細胞染色體變異及小鼠週邊血液紅血球微核等測試。結果顯示抗PRSV基因改造木瓜凍乾粉末(10倍濃縮)於2 mg/plate劑量下,無論有無添加肝臟活化酵素混合液(S9),對Salmonella Typhimurium TA98、TA100、TA102、TA1535及TA1537等5種菌株均無基因毒性作用。此外,於2 mg/ml劑量下不會造成中國倉鼠卵巢細胞染色體變異頻率增加。在微核試驗方面,單次給予2 g/kg劑量後48及72小時,並無觀察到綱織球抑制及綱織球微核率增加現象,綜合三種測試結果證實抗PRSV基因改造木瓜無基因毒性作用。動物毒理試驗則進行對大鼠口服急毒性及28天亞急毒性測試。於口服急毒性方面,2種單抗基因改造木瓜分別投予5 g/kg劑量,所有鼠隻無中毒症狀或死亡,顯示對大鼠之口服急毒性LD50值大於5 g/kg bw/day;28天亞急毒性試驗分別投予1 g/kg測試劑量,分析體重、飼料消耗量、血液學、血液生化學、尿液學及病理學等各項檢查,結果顯示各試驗組之飼料消耗量、血液學及尿液學與對照樣品組台農2號相比均無顯著差異,各處理組大鼠之體內重要器官均無明顯與試驗物質相關之肉眼及組織病理變化。綜合以上結果,抗PRSV基因改造木瓜(16-0-1及18-2-4)對大鼠之28天無毒害作用劑量(no observed adverse effect levels, NOAEL)大於1 g/kg bw/day,相當每人每天攝取600克新鮮木瓜,此NOAEL值依大鼠劑量換算至人體(HED)安全係數為5.4倍,約為國人每人每日攝取劑量(0.3 g/kg)之5倍劑量,顯示木瓜於一般攝取量下應屬安全。綜合以上結果,抗PRSV基因改造木瓜與親代母本木瓜(台農2號)實質等同安全。

Papaya (Carica papaya) is rich in vitamins and nutrition, and also an important fruit. However, it is suffered by papaya ringspot virus (PRSV) infection and causes severe damage in Taiwan. For this, a genetically modified (GM) papaya was newly developed by Prof. Yeh SD at NCHU that can be a valuable strategy to resistant PRSV infection. It was created by cloned the coat protein (CP) gene of PRSV that was transformed into confer resistance to PRSV. However, the edible safety of newly developed GM papaya is controversially. The aim of this study was conducted the safety assessments of six lyophilized samples from Tainon-2 (non-GM), 16-0-1 and 18-2-4 (GM) papaya fruit at green and ripe fruits by using genetic and animal toxicity assays. For the genotoxicity, including the Ames test of Salmonella typhimurium strain (TA98, TA100, TA102, TA1535, TA1537), the chromosomal aberration of Chinese hamster ovary (CHO cells) (in vitro) and micronucleus assays in mice (in vivo) were conducted. Results revealed that all papaya exhibited no mutagenicity to the tester strains of TA98, TA100, TA102, TA1535, TA1537 at a dose of 2 mg/plate these papaya with or without presence of S9 mixture. In addition, GM papaya at dose of 2 mg/ml did not increase the frequency of chromosomal aberration in CHO-K1 cells. Mice were single gavaged with 2 g/kg of GM papaya and observed the frequency of micronuclei at interval of 48 and 72 hrs. No inhibition on the reticulocytes or increase the ratio of micronuclei/reticulocytes in the peripheral blood was found in the papaya-treated mice. Results revealed that the lyophilized papaya fruits (10 folds condensation of raw) Tainon-2 (non-GM), 16-0-1 and 18-2-4 (GM) showed no genotoxicity either in vitro or in vivo by the toxicity assays of micronucleus test, chromosome aberration test and Ames tests. Furthermore, the acute and subacute oral toxicity feeding test of these papaya was also performed via oral gavage. All of tested lyophilized papaya had no acute toxicity at a maximal tested dose of 5 g/kg. The acute oral LD50 of GM papaya in rats was greater than 5 g/kg body weight. In the 28-day repeated oral toxicity test, all of tested papaya groups were detected for the change of food consumption, body weight gain, hematology, blood biochemical indices, organ weights and histopathology after daily gavaged maximal tested dose of 1 g/kg. Results revealed that no significant differences in the body weight gain, food consumption, hematology, blood biochemical indices, organ weights and histopathology between non-GM and GMs groups. Based on those results, the no observed adverse effect levels (NOAEL) of GM papaya (16-0-1 and 18-2-4) in rats was greater than 1 g/kg body weight, that equivalent to intake 600 grams per person per day of fresh papaya showed no toxicity. The NOAEL in rats, according to the conversion value, to the human equivalent doses (HED) safety factor of 5.4 times rat the average daily human consumption (0.3 g/kg) of fresh papaya fruit. It is suggested that GM papaya (16-0-1 and 18-2-4) under the in general intake is safe. In conclusion, the PRSV-resistant papaya fruit is comparable to the non-GM counterparts in terms of food safety.
URI: http://hdl.handle.net/11455/15401
其他識別: U0005-2707200912055500
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