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Evaluation of the antimutagenic effect of (-)-epegallocatechin gallate (EGCG) against chemical-induced mutagenesis of transgenic HITEC mice

(-)-表没食子儿茶素没食子酸酯 (EGCG) 对转基因 HITEC 小鼠化学诱导突变的抗突变作用评估

基本信息

批准号：
09672206
负责人：
YOKOI Tsuyoshi
金额：
$ 1.79万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

The antimutagenic activity of epegallocatechin gallate (EGCG), the major water soluble compound of green tea, against benzo[a]pyrene (B[a]P)-induced mutations were assessed by using transgenic mice carrying rpsL gene as a monitor of somatic mutations (HITEC mice). EGCG has been known to inhibit cytochrome P450. Male mice of 7 weeks old were given drinking water containing EGCG for 3 weeks. On day 7, mice were treated with a single i.p. injection of B[alpha]P (500 mg/kg bwt). Two weeks after the injection the mutaion of rpsL gene were analyzed. B[a]P treatment resulted in the significant approximately 4Ofold increase of mutation frequency in the lung of HITEC mice. Approximately 60% suppression of B[a]P-induced mutations in the lung was observed when mice were given EGCG at concentraions higher than 0.005% EGCG.B[alpha]P-induced mutations mainly occurred at G : C base-pairs. The majority of base substitutions were G : C*C : G transversions, followed by G : C*T : A transversions and G : C*A : T transitions. B[a]P-induced mutations frequently occurred in the several specific nucleotide sequences of the rpsL gene. These were AGC, CGC, CGT, TGC and CGT ; all of them contained guanine residue. B[a]P-induced mutaions seen in the mouse ras codon 12 or human p53 codon 157 were found in the rpsL gene, and that the mutations were suppressed by EGCG for B[alpha]P-induced mutagenesis in vivo suggest that the drinking of tea may reduce the tumor-initiating potency of B[a]P in the lung.

以携带rpsL基因的转基因小鼠（HITEC小鼠）为检测对象，研究了绿茶主要水溶性化合物没食子儿茶素没食子酸酯（EGCG）对苯并[a]芘（B[a]P）诱导突变的抗诱变活性。已知EGCG可抑制细胞色素P450。7周龄雄性小鼠连续3周饮用含有EGCG的水。第7天，小鼠单次腹腔注射B[α]P （500 mg/kg bwt）。注射2周后分析rpsL基因的突变情况。B[a]P处理导致HITEC小鼠肺部突变频率显著增加约4倍。当小鼠被给予浓度高于0.005%的EGCG时，观察到约60%的B[a] p诱导的肺突变被抑制。B[α] p诱导的突变主要发生在G: C碱基对。碱基取代以G: C*C: G迁移为主，其次是G: C*T: A迁移和G: C*A: T迁移。B[a] p诱导的突变经常发生在rpsL基因的几个特定核苷酸序列中。分别是AGC、CGC、CGT、TGC和CGT；它们都含有鸟嘌呤残留物。在小鼠ras密码子12和人p53密码子157中发现了B[a]P诱导的rpsL基因突变，EGCG在体内抑制了B[α]P诱导的突变，提示饮茶可能降低了B[a]P在肺中的致瘤能力。

项目成果

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Ayako Yamada, Ken-ichi Fujita, Tsuyoshi Yokoi, Shigeharu Muto, Akihiro Suzuki, Yoichi Gondoh, Motoya Katsuki and Tetsuya Kamataki: "In vivo detection of mutations induced by aflatoxin B1 using human CYP3A7/HITEC hybrid mice." Biochem.Biophys.Res.Com.250.

Ayako Yamada、Ken-ichi Fujita、Tsuyoshi Yokoi、Shigeharu Muto、Akihiro Suzuki、Yoichi Gondoh、Motoya Katsuki 和 Tetsuya Kamataki：“使用人 CYP3A7/HITEC 杂交小鼠体内检测黄曲霉毒素 B1 诱导的突变。”