论文部分内容阅读
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［４，５ｂ］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ＰｈＩＰＤＮＡ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ＰｈＩＰＤＮＡ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ＰｈＩＰＤＮＡ加合物形成的机理
Objective We have reported that drinking tea can effectively inhibit 2amino1methyl6phenylimidazo[4,5b]pyridine (PhIP) formation of carcinogenDNA adducts in rats. The aim is to explore this mechanism of action. Methods PhIP was metabolized and activated in vivo to form the final carcinogen N-acetoxy-PhIP. The latter was combined with DNA to form the PhIP-DNA adduct. This study simulated the in vivo conditions and observed the inhibitory effect of tea or tea polyphenols on the chemically synthesized [3H]N-acetoxy-PhIP and DNA reaction, and analyzed the reaction products by high-performance liquid chromatography. Results Both tea and tea polyphenols significantly inhibited the binding of PhIP to DNA. The inhibitory effect was in a concentration-effect relationship with the added tea or tea polyphenols. In the tested tea and tea polyphenols, the green tea inhibiting effect was better than that of black tea at the same concentration, and the green tea polyphenols were superior to the black tea polyphenols. High performance liquid chromatographic analysis did not find [3H]N-acetoxy-PhIP and tea polyphenols, and the main product in the reaction system was the parent heterocyclic amine PhIP. Conclusion The mechanism of tea polyphenols inhibiting the binding of NacetoxyPhIP and DNA is the direct reduction of NacetoxyPhIP to PhIP, which makes it lose its electrophilic ability and inhibit the formation of PhIPDNA adducts. Since both tea polyphenols and NacetoxyPhIP exist in the blood circulation and tissues, the direct reaction between the two may be the mechanism by which tea inhibits the formation of PhIPDNA adducts in vivo.