饮茶抑制大鼠体内杂环胺-DNA加合物形成的机理

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

Direct Detoxification of N acetoxy PhIP by Tea Polyphenols: A Possible Mechanism for Chemoprevention Against PhIP DNA Adduct Formation in Vivo

Objective We have shown that green tea inhibited food borne carcinogen 2 amino 1 methyl 6 phenylimidazo 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 N acetoxy PhIP with DNA. The reaction mixtures were analyzed by HPLC for the possible product(s) formed by the reaction of N acetoxy PhIP with tea polyphenols. Results It was found that agueous extract of tea and tea polyphenols strongly inhibited covalent binding of N acetoxy PhIP to DNA, and the inhibition was concentration dependent with respect to inhibitors. HPLC analyses of reaction mixture containing N acetoxy PhIP and tea polyphenols revealed the production of the parent amine, PhIP, indicating a redox mechanism. Conclusion In view of the presence of tea polyphenols in rat and human plasma after ingestion of tea, these results suggest that direct reduction of ultimate carcinogen N acetoxy PhIP by tea polyphenols is likely to be involved in the mechanism of chemoprevention of tea against PhIP DNA adduct formation in vivo.