title: Lycopene and beta-carotene protect against oxidative damage in HT29 cells at low concentrations but rapidly lose this capacity at higher doses.
abstract: Epidemiological studies have clearly demonstrated a link between dietary carotenoids and the reduced incidence of certain diseases, including some cancers. However recent intervention studies (e.g. ATBC, CARET and others) have shown that beta-carotene supplementation has little or no beneficial effect and may, in fact, increase the incidence of lung cancers in smokers. This presents a serious dilemma for the scientific community - are carotenoids at high concentrations actually harmful in certain circumstances? Currently, a significant number of intervention studies are on-going throughout the world involving carotenoids (of both natural and synthetic origin). Our approach has been to study the ability of supplementary carotenoids in protecting cells against oxidatively-induced DNA damage (as measured by the comet assay), and membrane integrity (as measured by ethidium bromide uptake). Both lycopene and beta-carotene only afforded protection against DNA damage (induced by xanthine/xanthine oxidase) at relatively low concentrations (1-3 microM). These levels are comparable with those seen in the plasma of individuals who consume a carotenoid-rich diet. However, at higher concentrations (4-10 microM), the ability to protect the cell against such oxidative damage was rapidly lost and, indeed, the presence of carotenoids may actually serve to increase the extent of DNA damage. Similar data were obtained when protection against membrane damage was studied. This would suggest that supplementation with individual carotenoids to significantly elevate blood and tissue levels is of little benefit and, may, in fact, be deleterious. This in vitro data presented maybe significant in the light of recent intervention trials.
authors: School of Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK. G.M.Lowe@Livjm.ac.uk
authors: G M
authors: GM
authors: Lowe
authors: L A
authors: LA
authors: Booth
authors: A J
authors: AJ
authors: Young
authors: R F
authors: RF
authors: Bilton
mesh_terms: D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D002338:Carotenoids / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004996:Ethidium; D019073:HT29 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000077276:Lycopene; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014343:Trypan Blue; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D019207:beta Carotene; D019820:Xanthine; D002338:Carotenoids; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D014969:Xanthine Oxidase; D004996:Ethidium; D014343:Trypan Blue; D000077276:Lycopene