Journal Article

Isoflavonoids and lignans have different potentials to modulate oxidative genetic damage in human colon cells

Beatrice L. Pool-Zobel, Herman Adlercreutz, Michael Glei, Ute M. Liegibel, Julie Sittlingon, Ian Rowland, Kristiina Wähälä and Gerhard Rechkemmer

in Carcinogenesis

Volume 21, issue 6, pages 1247-1252
Published in print June 2000 | ISSN: 0143-3334
Published online June 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.6.1247
Isoflavonoids and lignans have different potentials to modulate oxidative genetic damage in human colon cells

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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. H2O2-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 μM). The polyphenols (100 μM) did not reduce damage induced by 150 μM H2O2, indicating that they lacked antioxidative potential. At this concentration enterolactone also had no effect on intracellular oxidative stress induced by 31.25 and 125 μM H2O2. In contrast, enterolactone, dihydrogenistein and formononetin reduced endogenous oxidative DNA damage at 100 μM. Daily ingestion of nine slices (76.5 g/day) of rye crispbread per day (containing 41.8 and 33.0 μg/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 H2O2- induced damage are indicative of only marginal protective potential by antioxidant mechanisms. The genotoxic effects of genistein deserve further investigation.

Keywords: carbDCF, 6-carboxy-2′,7'-dichlorodihydrofluorescein diacetate; CLSM, confocal laser scanning microscopy; FCS, fetal calf serum; FRAP, ferric acid reducing activity of plasma; HBSS, Hank's balanced salt solution; LSM, laser scanning microscopy; ROI, regions of interest; ROS, reactive oxygen species.

Journal Article.  5595 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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