which include polychlorinated biphenyls (PCBs), dibenzofuSpecies-Specific Recombinant Cell Lines as Bioassay Systems rans (PCDFs), and dibenzo-p-dioxins (PCDDs) as well as for the Detection of 2,3,7,8-Tetrachlorodibenzo-p-dioxin-like many other subclasses of PCDHs (Giesy et al., 1994a). These known to bioaccumulate and biomagnify in the food chain Exposure to specific polychlorinated diaromatic hydrocarbons (Ballschmitter et al., 1989; Tanabe et al., 1987; Webster and (PCDH), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, di- Commoner, 1994; Giesy et al., 1994a,b). Exposure to and oxin), produces a wide variety of species-and tissue-specific toxic bioaccumulation of PCDHs has been observed to produce a and biological effects. Many of these responses are mediated by variety of species-and tissue-specific effects, such as tumor of PCDHs involve costly and time-consuming traditional instrumental analysis methods, such as gas chromatography Polychlorinated diaromatic hydrocarbons (PCDHs) 2 are a (GC) separation and mass spectrometry (MS). The identifidiverse group of widespread environmental contaminants, cation and quantification of these compounds is complicated by the fact that techniques and standards for identifying many of the congeners and isomers do not exist. In addition,

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Flavonoids are important bioactive dietary compounds. They induce electrophile-responsive element (EpRE)-mediated expression of enzymes, such as NAD(P)H-quinone oxidoreductase (NQO1) and glutathione S-transferases (GSTs), which are major defense enzymes against electrophilic toxicants and oxidative stress. The induction of EpRE-mediated gene transcription involves the release of the transcription factor Nrf2 from a complex with Keap1, either by a direct interaction of the inducer with Keap1 or by protein kinase C (PKC)-mediated phosphorylation of Nrf2. The inhibition of PKC in Hepa1c1c7 cells, stably transfected with human NQO1-EpRE-controlled luciferase revealed that PKC is not involved in flavonoid-induced EpRE-mediated gene transcription. However, the ability of flavonoids to activate an EpRE-mediated response correlates with their redox properties characterized by quantum mechanical calculations. Flavonoids with a higher intrinsic potential to generate oxidative stress and redox cycling are the most potent inducers of EpRE-mediated gene expression. Modulation of the intracellular glutathione (GSH) level showed that the EpRE-activation by flavonoids increased with decreasing GSH and vice versa, supporting an oxidative mechanism. In conclusion, the pro-oxidant activity of flavonoids can contribute to their health-promoting activity by inducing important detoxifying enzymes, pointing to a beneficial effect of a supposed toxic chemical reaction.

trum of possible biological actions of the bioactive compound quercetin is made using multiple gene expression analysis. Quercetin is a flavonoid that can inhibit proliferation of tumor cells and reduce the number of aberrant crypt foci, although increase of number of colon tumors was also reported. Aim of the study In order to elucidate possible mechanisms involved in its mode of action the effect of quercetin on expression of 4000 human genes in Caco-2 cells was studied and related to functional effects. Methods Caco-2 cells were exposed to 5 or 50 µM quercetin for 48 hours, differential expression of 4000 human genes was studied using microarrays and related to functional effects. Differentially expressed genes were categorized in seven functional groups: cell cycle and differentiation, apoptosis, tumor suppressor genes and oncogenes, cell adhesion and cell-cell interaction, transcription, signal transduction and energy metabolism. Also, cell proliferation and cell cycle distribution were measured. Results Quercetin (5 µM) downregulated expression of cell cycle genes (for example CDC6, CDK4 and cyclin D1), downregulated cell proliferation and induced cell cycle arrest in Caco-2 cells. After exposure to 50 µM quercetin cell proliferation decreased to 51.3 % of control, and further decrease of the percentage of cells in the G1 phase coincided with an increase of the percentage of cells in the sub-G1 phase. Quercetin upregulated expression of several tumor suppressor genes. In addition, genes involved in signal transduction pathways like beta catenin/ TCF signalling and MAPK signal transduction were influenced by quercetin. Conclusions This study shows that large-scale gene expression analysis in combination with functional assays yields a considerable amount of information on (anti-)carcinogenic potential of food components like quercetin.

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