Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/15437
標題: 三聚氰胺及三聚氰酸混合物之基因毒理及大鼠之腎臟排除研究
Study of the Genotoxicity and Elimination of the Melamine and Cyanuric Acid Mixture From the Kidney in Rats
作者: 吳依璇
Wu, Yi-Hsuan
關鍵字: melamine;三聚氰胺;cyanuric acid;crystal;genotoxicity;三聚氰酸;結晶;基因毒理
出版社: 獸醫病理生物學研究所
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摘要: 
2004年及2007年初,亞洲及北美地區陸續發生犬貓飼料含高量三聚氰胺及三聚氰酸引起犬貓腎衰竭案例。本實驗的目的為探討三聚氰胺及三聚氰酸的混合物經由生物轉化成有害物質。將三聚氰胺及三聚氰酸在1:1比例下進行,實驗觀察三聚氰胺與三聚氰酸混合物 (MC mixture) 形態學、基因毒性試驗及以高效液相色層分析法分析三聚氰胺在單次餵食MC mixture於腎臟的排除情形。型態學觀察中,MC mixture在不同溶劑中之結晶型態不同,組成比例也不同。在水中,結晶呈現細針尖狀,但在培養液中,結晶則呈現圓球形且有車軸狀輻射紋理,以掃描式電子顯微鏡觀察,前者結晶型態呈針狀,表面不平滑,後者呈球形,表面又有許多球形突出。以能量色散X射線 (EDX) 進行組成成分分析,在碳原子、氮原子、氧原子的組成比例上,水中MC mixture比例與標準式最接近,與從腎臟切片中結晶組成比例也相近,顯示腎臟中結晶成分與MC mixture類似。在基因毒理的試驗中,將混合物和Salmonella Typhimurium組胺酸突變株進行培養,在有或沒有肝臟酵素的作用下,皆沒有觀察到此突變株有回復突變之致基因變異性。在體外染色體結構變異試驗中,若受測物質具有基因毒性,則會使中國倉鼠卵巢細胞 (CHO-K1 cell) 之染色體產生變異,本實驗中觀察MC mixture對中國倉鼠卵巢細胞染色體並無異常頻率增加現象;而在小鼠周邊血液微核試驗中,無論在48小時或72小時之周邊血液,皆沒有明顯出現微核頻率增加之趨勢。在體內代謝速率方面,大鼠以三聚氰胺及三聚氰酸 (1:1) 混合灌食400 mg/kg,在灌食後第0.5、1、3、12、24、48小時分別犧牲,採取腎臟組織以高效液相層析法進行分析,結果顯示,灌食後第3小時腎臟中殘留三聚氰胺濃度達到最高,第12小時降低至高值之23%,其後繼續隨時間下降,顯示腎臟可排出大量的三聚氰胺,且清除速率快速。綜合以上結果,MC mixture並無致基因突變性,且於腎臟中排除快速,但造成病變的原因推測與結晶形成,阻塞並損傷腎小管上皮細胞有關。

In 2004 and early 2007, there were large outbreaks of high levels of melamine and cyanuric acid adulterated in the pet food in Asia and North America. The purpose of this study is to study the severity of the MC mixture toxicity converted to harmful substances by metabolism when melamine and cyanuric acid under 1:1 ratio. The study were to observe the MC mixture morphology, the genotoxicity test, and the high performance liquid chromatography (HPLC) to determine the melamine exclusion in the kidney. In the morphology observation, the deposits of melamine and cyanuric acid combining in D.W. were needle-like, fine, but when combining in cell culture medium, the shape of deposits changed into round and radial. Observe under scanning electron microscope (SEM), the former crystal was needle type and smooth, the later was spherical on the surface. It is believed that the accumulation or other physical properties of these insoluble crystals leading to the proximal tubular injuries in kidneys. The EDX showed the composition of the carbon, nitrogen and oxygen atom was close to the MC mixture in water and similar to crystalline in the kidney. In the genotoxicity test, the mixture was cultured with mutant Salmonella Typhimurium, with or without rat liver S9 mix; in the chromosome aberration test, Chinese hamster ovary cell lines (CHO-K1 cell lines) were used to detect the genotoxic substances. Results revealed that non of these two MC mixtures showed mutant potency; in the mouse peripheral blood micronucleus test, whether 48 or 72 hours, there were no significant increase in the micronucleus frequency. In the metabolic rate, SD rats feeding 400 mg/kg melamine and cyanuric acid, and the kidneys was analyzed after 0.5, 1, 3, 12, 24 and 48 hours after dosing. The results showed that the concentration in the kidney was the highest after 3 hours of the metabolise, and continue to decline over time. It showed most of the melamine was excretion by kidney and the clearance rate was high. Above all, MC mxture did not significantly induce gene mutation and excluded from kidney rapidly, the lesions caused by MC mixture related to crystal formation, tubular obstruction and tubular epithelial cell injury.
URI: http://hdl.handle.net/11455/15437
其他識別: U0005-2907201010135700
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