Dietary flavonoids protect human colonocyte DNA from oxidative attack in vitro
Dietary flavonoids protect human colonocyte DNA from oxidative attack in vitro
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DOI：
10.1007/s003940050043
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发表时间：
1999-02-01
影响因子：
5
通讯作者：
Dobson, VL
中科院分区：
文献类型：
--
作者：
Duthie, SJ;Dobson, VL
背景与目的：流行病学研究表明，人类饮食中的抗氧化多酚可以预防癌症等疾病。在本研究中，我们研究了类黄酮、槲皮素、杨梅素、山奈酚和芦丁对人结肠细胞体外氧化性 DNA 损伤的细胞保护潜力。方法：Caco-2 细胞具有特殊的肠上皮细胞/结肠细胞功能，被用作人结肠细胞的体外模型。使用过氧化氢作为氧化剂。 DNA 损伤（链断裂、氧化嘌呤和氧化嘧啶）使用碱性单细胞凝胶电泳或彗星测定法测定。测量了细胞生长和活力。结果：过氧化氢引起人类结肠细胞中 DNA 链断裂的剂量依赖性增加，可能是通过氧自由基的产生。槲皮素和杨梅素可保护 Caco-2 细胞免受氧化攻击。此外，槲皮素还能减少过氧化氢介导的生长抑制。芦丁和山奈酚均无效。然而，槲皮素在抑制 DNA 链断裂的同时，并没有改变过氧化物处理后氧化碱基的水平。抗真菌剂酮康唑可阻止 Caco-2 细胞中槲皮素的细胞保护作用，表明 P450 介导的代谢可能会改变类黄酮对抗 DNA 氧化损伤的功效。结论：类黄酮，尤其是人类饮食中最丰富的类黄酮槲皮素，可能在保护人类结肠细胞免受氧化攻击方面发挥重要作用。
Background & Aims: Epidemiological studies suggest that antioxidant polyphenols in the human diet may protect against diseases such as cancer. In this study we investigated the cytoprotective potential of the flavonoids, quercetin, myricetin, kaempferol and rutin against oxidative DNA damage in human colonocytes in vitro.Methods: Caco-2 cells, which display specialised enterocyte/colonocyte cell functions, were used as an in vitro model for human colonocytes. Hydrogen peroxide was employed as the oxidant. DNA damage (strand breakage, oxidised purines and oxidised pyrimidines) was determined using the alkaline single cell gel electrophoresis or comet assay. Cell growth and viability were measured.Results: Hydrogen peroxide caused a dose-dependent increase in DNA strand breakage in human colonocytes, presumably via oxygen free radical generation. Quercetin and myricetin protected Caco-2 cells against oxidative attack. In addition, quercetin decreased hydrogen peroxide-mediated inhibition of growth. Neither rutin nor kaempferol was effective. However, quercetin, while inhibiting DNA strand breakage, did not alter the levels of oxidised bases following peroxide treatment. The antifungal agent ketoconazole, prevented quercetin cytoprotection in Caco-2 cells, indicating that P450-mediated metabolism may alter the efficacy of the flavonoids against oxidative DNA damage.Conclusion: Flavonoids, particularly quercetin, the most abundant flavonoid in the human diet, are likely to be important in defending human colonocytes from oxidative attack.