紫草（Comfrey）在轉基因大藍鼠肺中導致的基因突變頻率和突變類型   全文下載

The Mutant Frequencies and Types of Mutations Induced by Comfrey in the Lungs of Transgenic Big Blue Rats

紫草（Symphytum Officinale）已經被當作蔬菜和草藥使用了很多年。然而，它是一個致突變和致癌物質。為了檢測紫草在大鼠肺中的誘變性及其作用機理，我們調查了紫草在大鼠肺中的基因突變頻率和突變類型。轉基因大藍鼠被連續12 個星期餵以含有8% 紫草根的食物。然后，我們檢測了大鼠肺中cII 轉基因的突變頻率和突變類型。試驗組的cII 突變頻率是48±9 × 10-6，而對照組cII 突變頻率是34±10 × 10-6，有顯著統計差異（p = 0.026）。試驗組和對照組的突變類型也是顯著不同的。在試驗組中，G:C → T:a 鹼基對替換（29%）是其主要類型的突變。然而，在對照組中，G:C → a:T 鹼基對替換（63%）是其主要的類型。另外，一異常類型的突變，雙鹼基對替換（4%），只出現在試驗組。G:C → T:a 和雙鹼基對替換已經被建議為咯里西啶類生物鹼致突變的標誌性類型。該實驗結果表明紫草是大鼠肺的致突變劑。紫草的誘變性主要源自于該植物中咯里西啶類生物鹼的遺傳毒性。

Comfrey (Symphytum Officinale) has been used as a vegetable and herbal remedy for many years. It, however, is a mutagen and carcinogen in liver and a possible genotoxin in lung. In order to evaluate the mutagenicity of comfrey and the mechanisms of action in rat lung, we examined the mutant frequencies (MF) and mutational types in the lung cII gene from transgenic Big Blue rats treated with 8% comfrey for 12 weeks. The cII MF in the lungs for rats fed with comfrey was 48 ± 9 × 10-6, which was significantly greater than the MF for control rats, 34 ± 10 × 10-6 (p = 0.026). The mutational spectrum in lung from comfrey-fed rats is significantly different from that in the control. G:C → T:A transversion (29%) was the major type of mutation in comfrey-fed rats, whereas G:C → A:T transition (63%) was the predominant mutation in the controls. An unusual type of tandem–base substitution (4%) was observed among the mutations from comfrey-fed rats that were not seen in the control. This type of tandem-base substitution has been suggested as a mutational signature for the genetic damage of pyrrolizidine alkaloids (PAs). The results indicate that comfrey is mutagenic in rat lung and the types of mutations induced by comfrey are similar to those by other PAs; and suggest that the mutagenicity of comfrey in rat lung results from the genotoxicity of PAs in the plant.