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大鼠器官外植体培养物中鞣花酸的代谢及其与DNA的结合

Ellagic acid metabolism and binding to DNA in organ explant cultures of the rat.

作者信息

Teel R W, Martin R M, Allahyari R

出版信息

Cancer Lett. 1987 Aug;36(2):203-11. doi: 10.1016/0304-3835(87)90092-9.

Abstract

Ellagic acid (EA) is a plant phenolic compound with postulated antimutagenic and anticarcinogenic activity. In this study, explants of esophagus, forestomach, colon, bladder, trachea, lung and liver from male Sprague-Dawley rats (130-140 g) were incubated in culture medium containing [3H]EA (20 microM, 4.5 microCi/ml) for 24 h at 37 degrees C. After extraction, purification and quantitation of explant DNA significant differences in the binding of EA to the DNA was observed. The most binding occurred in esophagus and the least in lung. Analysis of the organsoluble fraction of the culture medium by high performance liquid chromatography yielded 3 metabolites of EA. None of the metabolites were identified. Elution of water-soluble metabolites from an alumina column showed that there were sulfate ester, glucuronide and glutathione conjugates of EA in the explant culture medium from all the organs. The profile of water-soluble conjugates was very similar between colon and forestomach and between trachea and lung. These results indicate that EA binds to DNA in different tissues and that tissues metabolize EA to both organosoluble and water-soluble products.

摘要

鞣花酸(EA)是一种具有假定抗诱变和抗癌活性的植物酚类化合物。在本研究中,将雄性Sprague-Dawley大鼠(130 - 140克)的食管、前胃、结肠、膀胱、气管、肺和肝脏外植体在含有[3H]EA(20微摩尔,4.5微居里/毫升)的培养基中于37℃孵育24小时。在对外植体DNA进行提取、纯化和定量后,观察到EA与DNA的结合存在显著差异。结合最多的是食管,最少的是肺。通过高效液相色谱法分析培养基的有机可溶部分,得到了EA的3种代谢产物。未鉴定出任何代谢产物。从氧化铝柱上洗脱水溶性代谢产物表明,所有器官的外植体培养基中都存在EA的硫酸酯、葡萄糖醛酸和谷胱甘肽共轭物。结肠和前胃之间以及气管和肺之间的水溶性共轭物谱非常相似。这些结果表明,EA在不同组织中与DNA结合,并且组织将EA代谢为有机可溶和水溶性产物。

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