Pool-Zobel B L, Adlercreutz H, Glei M, Liegibel U M, Sittlingon J, Rowland I, Wähälä K, Rechkemmer G
Department of Nutritional Toxicology, Institute for Nutrition, Friedrich Schiller University, Dornburger Strabetae 25, 07743 Jena, Germany.
Carcinogenesis. 2000 Jun;21(6):1247-52.
Polyphenolic compounds, including isoflavonoids and lignans, have been suggested to be chemopreventive on account of antioxidative properties. In this context it is of importance to have knowledge of their ability to reduce oxidative stress within target cells of tumorigenesis. Therefore, we investigated isoflavonoids and lignans for modulation of oxidative genetic damage in mammalian cells. H(2)O(2)-induced damage as well as endogenous DNA strand breaks and oxidized bases were determined after 30 min incubation of human colon cells with polyphenols using various modifications of the microgel electrophoresis assay (Comet assay). Enterolactone, a mammalian metabolite of plant lignans, was additionally investigated for modulation of intracellular oxidative stress in NIH 3T3 cells using laser scanning microscopy. In vivo effects of rye crispbread (a source of lignans) were investigated in 12 human volunteers by determining genetic damage in lymphocytes and antioxidant activity in plasma (FRAP assay). Genistein induced DNA breaks in the human tumour cell line HT29 clone 19A (12.5-100 microM). The polyphenols (100 microM) did not reduce damage induced by 150 microM H(2)O(2), indicating that they lacked antioxidative potential. At this concentration enterolactone also had no effect on intracellular oxidative stress induced by 31.25 and 125 microM H(2)O(2). In contrast, enterolactone, dihydrogenistein and formononetin reduced endogenous oxidative DNA damage at 100 microM. Daily ingestion of nine slices (76.5 g/day) of rye crispbread per day (containing 41.8 and 33.0 microg/100 g dry weight secoisolariciresinol and matairesinol, respectively) for 2 weeks did not significantly reduce genetic damage in blood lymphocytes, nor was there a modulation of plasma antioxidant capacity. The moderate effects of high concentrations of the tested compounds on endogenous oxidative DNA damage and failure to prevent H(2)O(2)- induced damage are indicative of only marginal protective potential by antioxidant mechanisms. The genotoxic effects of genistein deserve further investigation.
包括异黄酮和木脂素在内的多酚类化合物，因其抗氧化特性而被认为具有化学预防作用。在这种情况下，了解它们降低肿瘤发生靶细胞内氧化应激的能力非常重要。因此，我们研究了异黄酮和木脂素对哺乳动物细胞氧化遗传损伤的调节作用。使用微凝胶电泳分析（彗星试验）的各种改进方法，在人结肠细胞与多酚孵育30分钟后，测定H₂O₂诱导的损伤以及内源性DNA链断裂和氧化碱基。此外，使用激光扫描显微镜研究了植物木脂素的哺乳动物代谢产物肠内酯对NIH 3T3细胞内氧化应激的调节作用。通过测定淋巴细胞中的遗传损伤和血浆中的抗氧化活性（FRAP试验），研究了黑麦脆饼（木脂素的来源）对12名人类志愿者的体内影响。染料木黄酮在人肿瘤细胞系HT29克隆19A（12.5 - 100 microM）中诱导DNA断裂。多酚（100 microM）并未降低150 microM H₂O₂诱导的损伤，表明它们缺乏抗氧化潜力。在此浓度下，肠内酯对31.25和125 microM H₂O₂诱导的细胞内氧化应激也没有影响。相比之下，肠内酯、二氢染料木黄酮和芒柄花黄素在100 microM时可减少内源性氧化DNA损伤。每天食用九片（76.5克/天）黑麦脆饼（分别含有41.8和33.0微克/100克干重的开环异落叶松脂素和罗汉松脂素），持续2周，并未显著降低血液淋巴细胞中的遗传损伤，血浆抗氧化能力也没有受到调节。高浓度测试化合物对内源性氧化DNA损伤的适度影响以及未能预防H₂O₂诱导的损伤表明，抗氧化机制的保护潜力仅为边际性。染料木黄酮的遗传毒性作用值得进一步研究。
