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Dietary Berries and Ellagic Acid Prevent Oxidative DNA Damage and Modulate Expression of DNA Repair Genes
James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA
Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY 40202, USA
Division of Population Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
* Author to whom correspondence should be addressed.
Received: 17 January 2008; Accepted: 1 February 2008 / Published: 12 March 2008
Abstract: DNA damage is a pre-requisite for the initiation of cancer and agents that reduce this damage are useful in cancer prevention. In this study, we evaluated the ability of whole berries and berry phytochemical, ellagic acid to reduce endogenous oxidative DNA damage. Ellagic acid was selected based on >95% inhibition of 8-oxodeoxyguosine (8-oxodG) and other unidentified oxidative DNA adducts induced by 4-hydroxy-17ß-estradiol and CuCl2 in vitro. Inhibition of the latter occurred at lower concentrations (10 μM) than that for 8-oxodG (100 μM). In the in vivo study, female CD-1 mice (n=6) were fed either a control diet or diet supplemented with ellagic acid (400 ppm) and dehydrated berries (5% w/w) with varying ellagic acid contents – blueberry (low), strawberry (medium) and red raspberry (high), for 3 weeks. Blueberry and strawberry diets showed moderate reductions in endogenous DNA adducts (25%). However, both red raspberry and ellagic acid diets showed a significant reduction of 59% (p <0.001) and 48% (p < 0.01), respectively. Both diets also resulted in a 3-8 fold over-expression of genes involved in DNA repair such as xeroderma pigmentosum group A complementing protein (XPA), DNA excision repair protein (ERCC5) and DNA ligase III (DNL3). These results suggest that red raspberry and ellagic acid reduce endogenous oxidative DNA damage by mechanisms which may involve increase in DNA repair.
Keywords: 4-Hydroxy estradiol; DNA damage and repair; dietary intervention; edible berries; raspberries; ellagic acid; polyphenols; 32P-postlabeling.
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Aiyer, H.S.; Vadhanam, M.V.; Stoyanova, R.; Caprio, G.D.; Clapper, M.L.; Gupta, R.C. Dietary Berries and Ellagic Acid Prevent Oxidative DNA Damage and Modulate Expression of DNA Repair Genes. Int. J. Mol. Sci. 2008, 9, 327-341.
Aiyer HS, Vadhanam MV, Stoyanova R, Caprio GD, Clapper ML, Gupta RC. Dietary Berries and Ellagic Acid Prevent Oxidative DNA Damage and Modulate Expression of DNA Repair Genes. International Journal of Molecular Sciences. 2008; 9(3):327-341.
Aiyer, Harini S.; Vadhanam, Manicka V.; Stoyanova, Radka; Caprio, Gerard D.; Clapper, Margie L.; Gupta, Ramesh C. 2008. "Dietary Berries and Ellagic Acid Prevent Oxidative DNA Damage and Modulate Expression of DNA Repair Genes." Int. J. Mol. Sci. 9, no. 3: 327-341.