利用動物模式研究中草藥成分對化學致癌物誘發DNA損傷與基因突變之拮抗作用
江素瑛
中國醫藥學
癌症為國人重要死亡原因，尋求治療與預防癌症的藥物乃是當代醫學重要的課題。近年來的研究已證實化學基因致癌物或其衍生物可與DNA反應形成DNA共價鍵結物(DNA adducts)，其在DNA 複製時可能會引起基因突變，進而引發癌症。此DNA損傷與基因突變已被公認為化學基因致癌物癌化過程中的起始因子，所以抑制DNA損傷與基因突變可能可達到抗癌防癌之目的。本計畫擬建立與利用化學基因致癌物誘發的DNA損傷與基因突變之動物模式，供研究可降低DNA損傷或基因突變進而用於抗癌防癌的中藥，並進一步探討其可能作用機轉。并沒食子酸（ellagic acid, EA）或表沒食子兒茶素表沒食子酸酯（(-)-epigallocatechin gallate, EGCG）為已知具有抗癌作用的中藥抽提物之單離成分，然其作用機轉尚不清楚。我們將小鼠經腹腔注射化學致癌物乙基亞硝酸基尿素（ethylnitrosourea, ENU）以作對照組，另外兩組小鼠預飼EA和EGCG七天後再投于ENU，或中藥抽提物(EA和EGCG)與ENU同時給與小鼠。一批老鼠在投于ENU之二小時後犧牲，取出肝臟以萃取DNA，用新發展完成之高敏感度與專屬性的氣相層析儀加質譜儀（GC/MS）方法定量分析ENU誘發的DNA adduct 7-ethyl guanine。另外一批老鼠在投于ENU之二十八天後犧牲，取出脾臟分離淋巴細胞，培養在選擇性試劑(6-thioguanine)中十天，以計算hprt基因的突變機率。結果若顯示中藥的單離成分有減低ENU所誘發DNA損傷與hprt基因突變的效果，即有抗基因毒性與抗癌防癌的功能。本年度計畫將使用中藥抽提物之單離成分以驗證此動物模式，希望在後續計畫中，繼續利用這個動物模式探討各種中藥單劑與複方之抗癌防癌效果。
關鍵字：抗基因損傷與突變作用、DNA共價鍵結物、hprt突變機率
The use of an animal model to study the protective effects of the ingredients of Chinese herbal medicines on chemical-induced DNA damage and mutations
Su-yin Chiang
Institute of Chinese Medical Science at China Medical College
Cancer is the leading death cause in Taiwan. It becomes an urgent issue to search for medicines against cancer. Recent studies have demonstrated that genotoxic chemicals or their derivatives can interact with DNA to form DNA adducts, which may cause mutations during DNA replication and subsequently lead to cancer development. DNA adducts and mutations are considered as early indicators in the pathogenesis of carcinogenesis. Medicines that could inhibit the formation of DNA adducts and mutations might suggest their potential in cancer prevention. In this study, we plan to develop an animal model to investigate the protective effects of the ingredients of Chinese herbal medicines on genotoxicant-induced DNA damage and mutations. Ellagic acid or (-)-epigallocatechin gallate (EGCG), isolated ingredients from Chinese herbal medicines, are known to possess anti-carcinogenic effects in rodents. However, their underlined mechanism in cancer prevention remains unclear. Mice will be orally fed w
關鍵字：Anti-genotoxic effects, DNA adduct, hprt mutation frequency
