Dietary berries and ellagic acid prevent oxidative DNA damage and modulate expression of DNA repair genes.
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 CuCl(2) in vitro. Inhibition of the latter occurred at lower concentrations (10 microM) than that for 8-oxodG (100 microM). 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.
Aiyer
Harini S
HS
James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Vadhanam
Manicka V
MV
0000-0003-0727-9983
James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Stoyanova
Radka
R
Division of Population Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Caprio
Gerard D
GD
Division of Population Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Clapper
Margie L
ML
Division of Population Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Gupta
Ramesh C
RC
James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.