title: Cytotoxicity, genotoxicity and oxidative reactions in cell-culture models: modulatory effects of phytochemicals.
abstract: Much research effort has focused on the identification of phytochemicals in fruit and vegetables which exert beneficial effects. Our research examines modulatory effects of phytochemicals on cytotoxicity, genotoxicity and oxidative reactions in cell systems. Two examples of our studies are discussed. First, the potential beneficial effects of flavonoids are demonstrated. Flavonoids are reported to exhibit a wide variety of biological effects, including antioxidant and free-radical-scavenging activities. The aim of the study was to determine if flavonoids could protect against H2O2-induced DNA damage, as measured by the comet assay, in Caco-2 and HepG2 cells. Both cell lines were supplemented with increasing concentrations of myricetin, quercetin and rutin for 24 h followed by exposure to H2O2 (50 microM) for 30 min. Exposure to H2O2 for 30 min at 37 degrees C resulted in significant DNA damage and pre-incubation with the flavonoids before H2O2 exposure significantly (P <0.05) protected Caco-2 and HepG2 cells against H2O2-induced DNA damage. Secondly, we illustrate the use of cellular models to study oxysterol-induced toxicity. Oxysterols are generated during the cooking and processing of foods and may be produced endogenously by the oxidation of membrane lipids. Recent findings suggest that oxysterols may modulate cytotoxicity by exerting effects on the induction of apoptosis. 7beta-Hydroxycholesterol (7beta-OHC) and 25-hydroxycholesterol, both of which are commonly found in foods, were investigated for their abilities to induce apoptosis in a human monocytic blood cell line, U937, and in the human hepatoma cell line, HepG2 cells. U937 and HepG2 cells were incubated for up to 48 h with 30 microM oxysterol. 7beta-OHC induced apoptosis in U937 cells as measured by non-random DNA fragmentation, condensed and fragmented nuclei, and the generation of hypodiploid cells. In contrast, oxysterols may induce cell death by a different mechanism in the hepatoma cells, possibly by necrosis.
authors.affiliation: Nutritional Sciences, Department of Food Science and Technology, University College, Cork, Ireland.
authors.forename: N M
authors.initials: NM
authors.lastname: O'Brien
authors.forename: J A
authors.initials: JA
authors.lastname: Woods
authors.forename: S A
authors.initials: SA
authors.lastname: Aherne
authors.forename: Y C
authors.initials: YC
authors.lastname: O'Callaghan
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000494:pharmacology; D009336:Necrosis; D010100:Oxygen / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology; D012431:Rutin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D020298:U937 Cells
chemical_list: D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D000975:Antioxidants; D005419:Flavonoids; D006888:Hydroxycholesterols; D010936:Plant Extracts; C011724:cholest-5-en-3 beta,7 alpha-diol; D012431:Rutin; C007997:25-hydroxycholesterol; C040015:myricetin; D011794:Quercetin; D006861:Hydrogen Peroxide; D010100:Oxygen