{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T21:26:45Z","timestamp":1788557205800,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2008,3,12]],"date-time":"2008-03-12T00:00:00Z","timestamp":1205280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 &gt;95% inhibition of 8-oxodeoxyguosine (8-oxodG) and other unidentified oxidative DNA adducts induced by 4-hydroxy-17\u00df-estradiol and CuCl2 in vitro. Inhibition of the latter occurred at lower concentrations (10 \u03bcM) than that for 8-oxodG (100 \u03bcM). 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 \u2013 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 <\/jats:p>","DOI":"10.3390\/ijms9030327","type":"journal-article","created":{"date-parts":[[2008,12,1]],"date-time":"2008-12-01T09:42:49Z","timestamp":1228124569000},"page":"327-341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Dietary Berries and Ellagic Acid Prevent Oxidative DNA Damage and Modulate Expression of DNA Repair Genes"],"prefix":"10.3390","volume":"9","author":[{"given":"Harini S.","family":"Aiyer","sequence":"first","affiliation":[{"name":"James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0727-9983","authenticated-orcid":false,"given":"Manicka V.","family":"Vadhanam","sequence":"additional","affiliation":[{"name":"James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radka","family":"Stoyanova","sequence":"additional","affiliation":[{"name":"Division of Population Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard D.","family":"Caprio","sequence":"additional","affiliation":[{"name":"Division of Population Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margie L.","family":"Clapper","sequence":"additional","affiliation":[{"name":"Division of Population Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh C.","family":"Gupta","sequence":"additional","affiliation":[{"name":"James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2008,3,12]]},"reference":[{"key":"ref_1","unstructured":"ACS (2007). Cancer Facts and Figures-2007, American Cancer Society."},{"key":"ref_2","first-page":"40","article-title":"Is estradiol a genotoxic mutagenic carcinogen?","volume":"21","author":"Liehr","year":"2000","journal-title":"Endocr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jsbmb.2006.06.019","article-title":"Induction of A.T to G.C mutations by erroneous repair of depurinated DNA following estrogen treatment of the mammary gland of ACI rats","volume":"101","author":"Mailander","year":"2006","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/oxfordjournals.jncimonographs.a024241","article-title":"Developmental, cellular, and molecular basis of human breast cancer","volume":"27","author":"Russo","year":"2000","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1093\/carcin\/15.7.1421","article-title":"DNA damage caused by reactive oxygen species originating from a copper-dependent oxidation of the 2-hydroxy catechol of estradiol","volume":"15","author":"Li","year":"1994","journal-title":"Carcinogenesis"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/oxfordjournals.jncimonographs.a024245","article-title":"Endogenous estrogens as carcinogens through metabolic activation","volume":"27","author":"Yager","year":"2000","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1093\/carcin\/22.9.1573","article-title":"Catechol estrogen metabolites and conjugates in mammary tumors and hyperplastic tissue from estrogen receptor-alpha knock-out (ERKO)\/Wnt-1 mice: implications for initiation of mammary tumors","volume":"22","author":"Devanesan","year":"2001","journal-title":"Carcinogenesis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S0960-0760(03)00377-7","article-title":"Genotoxic metabolites of estradiol in breast: potential mechanism of estradiol induced carcinogenesis","volume":"86","author":"Yue","year":"2003","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/S0891-5849(02)00826-2","article-title":"Free radical-induced damage to DNA: mechanisms and measurement","volume":"32","author":"Dizdaroglu","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1021\/tx000131d","article-title":"An improved (32)P-postlabeling assay for the sensitive detection of 8-oxodeoxyguanosine in tissue DNA","volume":"14","author":"Gupta","year":"2001","journal-title":"Chem. Res. Toxicol."},{"key":"ref_11","unstructured":"Gupta, RC, Ravoori, S, and Vadhanam, MV (,  2003). In Adducteomics-Novel subgroups of DNA adducts detected in human tissues. Proc. Am. Assn. Can. Res, Washington DC."},{"key":"ref_12","first-page":"1437","article-title":"Modulation of novel DNA adducts during human uterine cervix cancer progression","volume":"29","author":"Ravoori","year":"2006","journal-title":"Int. J. Oncol."},{"key":"ref_13","unstructured":"Gupta, RC, Ravikuma, MNV, Vadhanam, MV, and Arif, JM (2001). In Detection of Oxidatively damaged Polar DNA adducts by 32P-postlabeling."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/1097-0215(20010101)91:1<132::AID-IJC1019>3.0.CO;2-6","article-title":"1,2-dithiole-3-thione and its structural analogue oltipraz are potent inhibitors of dibenz","volume":"91","author":"Smith","year":"2001","journal-title":"Int. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0027-5107(01)00173-7","article-title":"Effect of chemopreventive agents on DNA adduction induced by the potent mammary carcinogen dibenzo[a,l]pyrene in the human breast cells MCF-7","volume":"480\u2013481","author":"Smith","year":"2001","journal-title":"Mutat. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0027-5107(98)00244-9","article-title":"Determining efficacy of cancer chemopreventive agents using a cell-free system concomitant with DNA adduction","volume":"425","author":"Smith","year":"1999","journal-title":"Mutat. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/0889-1575(89)90005-7","article-title":"Extraction, stability and quantitation of ellagic acid in various fruits and nuts","volume":"2","author":"Daniel","year":"1989","journal-title":"J. Food Composition and Analysis"},{"key":"ref_18","first-page":"235","article-title":"Induction of uterine adenocarcinoma in CD-1 mice by catechol estrogens","volume":"60","author":"Newbold","year":"2000","journal-title":"Cancer Res."},{"key":"ref_19","first-page":"983","article-title":"A rapid screening assay for antioxidant potential of natural and synthetic agents in vitro","volume":"20","author":"Srinivasan","year":"2002","journal-title":"Int. J. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1093\/carcin\/7.10.1663","article-title":"Disposition of the naturally occurring antimutagenic plant phenol, ellagic acid, and its synthetic derivatives, 3-O-decylellagic acid and 3,3\u2032-di-O-methylellagic acid in mice","volume":"7","author":"Smart","year":"1986","journal-title":"Carcinogenesis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/ijc.1193","article-title":"Catechol estrogens induce oxidative DNA damage and estradiol enhances cell proliferation","volume":"92","author":"Hiraku","year":"2001","journal-title":"Int. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1021\/tx025650q","article-title":"Hydroxyl radical is not the main reactive species involved in the degradation of DNA bases by copper in the presence of hydrogen peroxide","volume":"16","author":"Frelon","year":"2003","journal-title":"Chem. Res. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1093\/carcin\/22.8.1239","article-title":"Site specificity and mechanism of oxidative DNA damage induced by carcinogenic catechol","volume":"22","author":"Oikawa","year":"2001","journal-title":"Carcinogenesis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1021\/tx960103o","article-title":"Oxidative DNA damage induced by activation of polychlorinated biphenyls (PCBs): implications for PCB-induced oxidative stress in breast cancer","volume":"9","author":"Oakley","year":"1996","journal-title":"Chem. Res. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1042\/bj2730601","article-title":"Copper-ion-dependent damage to the bases in DNA in the presence of hydrogen peroxide","volume":"273","author":"Aruoma","year":"1991","journal-title":"Biochem. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8039","DOI":"10.1073\/pnas.83.21.8039","article-title":"Inhibition of N-methyl-N-nitrosourea-induced mutagenicity and DNA methylation by ellagic acid","volume":"83","author":"Dixit","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/0304-3835(86)90058-3","article-title":"Ellagic acid binding to DNA as a possible mechanism for its antimutagenic and anticarcinogenic action","volume":"30","author":"Teel","year":"1986","journal-title":"Cancer Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1093\/carcin\/9.7.1313","article-title":"Inhibition of N-nitrosobenzylmethylamine metabolism and DNA binding in cultured rat esophagus by ellagic acid","volume":"9","author":"Mandal","year":"1988","journal-title":"Carcinogenesis"},{"key":"ref_29","first-page":"2951","article-title":"Inhibition of benzo(a)pyrene and benzo(a)pyrene-trans-7,8-diol metabolism and DNA binding in mouse lung explants by ellagic acid","volume":"45","author":"Dixit","year":"1985","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1093\/carcin\/8.11.1651","article-title":"Inhibition of aflatoxin B1 mutagenesis in Salmonella typhimurium and DNA damage in cultured rat and human tracheobronchial tissues by ellagic acid","volume":"8","author":"Mandal","year":"1987","journal-title":"Carcinogenesis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4069","DOI":"10.1021\/jf060300l","article-title":"Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption","volume":"54","author":"Wu","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1093\/carcin\/17.4.821","article-title":"The effects of dietary ellagic acid on rat hepatic and esophageal mucosal cytochromes P450 and phase II enzymes","volume":"17","author":"Ahn","year":"1996","journal-title":"Carcinogenesis"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/carcin\/11.1.55","article-title":"Inhibition of N-nitrosobenzylmethylamine-induced esophageal tumorigenesis in rats by ellagic acid","volume":"11","author":"Mandal","year":"1990","journal-title":"Carcinogenesis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/carcin\/22.3.441","article-title":"Inhibition of N-nitrosomethylbenzylamine-induced tumorigenesis in the rat esophagus by dietary freeze-dried strawberries","volume":"22","author":"Carlton","year":"2001","journal-title":"Carcinogenesis"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1076\/phbi.40.7.43.9174","article-title":"The effect of freeze-dried blueberries on N-nitrosomethylbenzylamine tumorigenesis in the rat esophagus","volume":"40","author":"Aziz","year":"2002","journal-title":"Pharmaceutical Biology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1021\/jf9908345","article-title":"Antioxidant activity in fruits and leaves of blackberry, raspberry, and strawberry varies with cultivar and developmental stage","volume":"48","author":"Wang","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","first-page":"1025","article-title":"Hepatoprotective activity of ellagic acid against carbon tetrachloride induced hepatotoxicity in rats","volume":"37","author":"Singh","year":"1999","journal-title":"Indian J. Exp. Biol."},{"key":"ref_38","first-page":"363","article-title":"Inhibition of liver fibrosis by ellagic acid","volume":"40","author":"Thresiamma","year":"1996","journal-title":"Indian J. Physiol. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1191\/096032799678839563","article-title":"Ellagic acid ameliorates nickel induced biochemical alterations: diminution of oxidative stress","volume":"18","author":"Ahmed","year":"1999","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1615\/JEnvPathToxOncol.v23.i3.50","article-title":"Prevention and repair of DNA damage by selected phytochemicals as measured by single cell gel electrophoresis","volume":"23","author":"Chakraborty","year":"2004","journal-title":"J. Environ. Pathol. Toxicol. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0027-5107(01)00073-2","article-title":"Role of plant polyphenols in genomic stability","volume":"475","author":"Ferguson","year":"2001","journal-title":"Mutat. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1207\/s15327914nc5401_14","article-title":"Markers of oxidative DNA damage in human interventions with fruit and berries","volume":"54","author":"Freese","year":"2006","journal-title":"Nutr. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Pfeifer, P (1996). Technologies for Detection of DNA Damage and Mutations, Plenum Press.","DOI":"10.1007\/978-1-4899-0301-3"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Aiyer, HS, Srinivasan, C, and Gupta, RC (2008). Dietary berries and ellagic acid diminish estrogen-mediated mammary tumors in ACI rats. Nutr. Cancer, (in press).","DOI":"10.1080\/01635580701624712"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1093\/jn\/123.11.1939","article-title":"AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet","volume":"123","author":"Reeves","year":"1993","journal-title":"J. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"872","DOI":"10.2144\/01314mt04","article-title":"ArrayExplorer, a program in Visual Basic for robust and accurate filter cDNA array analysis","volume":"31","author":"Patriotis","year":"2001","journal-title":"Biotechniques"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/9\/3\/327\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T22:20:42Z","timestamp":1760221242000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/9\/3\/327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,3,12]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2008,3]]}},"alternative-id":["i9030327"],"URL":"https:\/\/doi.org\/10.3390\/ijms9030327","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,3,12]]}}}