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饮茶抑制大鼠体内杂环胺 |
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林东昕1 Fred F.Kadlubar2 陈君石3
【摘要】 目的 我们已报告饮茶可有效抑制2-氨基-1-甲基-6-苯基咪唑并［4,5-b］吡啶(PhIP)在大鼠体内形成致癌物-DNA加合物，本研究旨在探讨这一作用机理。方法 PhIP在体内经代谢活化形成终致癌物N-乙酰氧基-PhIP，后者与DNA结合形成PhIP-DNA加合物。本研究模拟体内条件，观察茶水或茶多酚对化学合成的［3H］N-乙酰氧基-PhIP与DNA反应的抑制作用，并以高效液相色谱分析反应产物。结果 茶水和茶多酚均可显著抑制PhIP与DNA结合，抑制效果与加入的茶水或茶多酚呈浓度-效应关系。在所测试的茶水和茶多酚中，在同等浓度下，绿茶抑制效果优于红茶，绿茶多酚优于红茶多酚。高效液相色谱分析未发现［3H］N-乙酰氧基-PhIP与茶多酚的结合物，而反应体系中的主要产物是母体杂环胺PhIP。结论 茶多酚抑制N-乙酰氧基-PhIP与DNA结合的作用机理，是直接将N-乙酰氧基-PhIP还原成PhIP，使之失去亲电子的能力从而抑制PhIP-DNA加合物形成。鉴于茶多酚和N-乙酰氧基-PhIP均可在血循环和组织中存在，两者之间的直接反应可能是饮茶抑制体内PhIP-DNA加合物形成的机理。
【关键词】 茶 2-氨基-1-甲基-6-苯基咪唑并［4,5-b］吡啶 DNA加合物
Direct Detoxification of N-acetoxy-PhIP by Tea Polyphenols: A Possible Mechanism for Chemoprevention Against PhIP-DNA Adduct Formation in Vivo
Lin Dongxin*, Fred F. Kadlubar, Chen Junshi. *Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021
【Abstract】 Objective We have shown that green tea inhibited food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo ［4,5-b］ pyridine (PhIP)-induced carcinogen-DNA adduct formation in rats, and this protective effect of tea appears not relote to the modifications of metabolic enzymes involved in PhIP metabolism. The aim of this study was to explore the direct reaction of tea and tea polyphenols with N-acetoxy-PhIP, an ultimate carcinogen of PhIP formed via metabolic activation. Methods DNA binding assays were conducted to examine the effect of aqueous extract of tea and tea polyphenols on the reaction of ［3H］N-acetoxy-PhIP with DNA. The reaction mixtures were analyzed by HPLC for the possible product(s) formed by the reaction of ［3H］N-acetoxy-PhIP with tea polyphenols. Results It was found that agueous extract of tea and tea polyphenols strongly inhibited covalent binding of ［3H］N-acetoxy-PhIP to DNA, and the inhibition was concentration-dependent with respect to inhibitors. HPLC analyses of reaction mixture containing ［3H］N-acetoxy-P[1] [2] [3] 下一页
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