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Rats in group 1 (control group) received a single intraperitoneal (i.p.) injection of normal saline. Animals in group 2 were given ginger (50 mg\/kg\/day) in drinking water for 8 weeks. Rats in group 3 (DEN group) were injected with a single dose of DEN (200 mg\/kg, i.p.), 2 weeks later received a single dose of CCl<jats:sub>4<\/jats:sub> (2 mL\/kg i.g) by gavage as 1:1 dilution in corn oil. Animals in group 4 (DEN\u2010ginger group) received the same carcinogenesis induction protocol as in group 3 plus ginger (50 mg\/kg\/day) in drinking water for 2 weeks before induction of hepatocarcinogenesis and continued throughout the experimental period. DEN\u2010initiated and CCl<jats:sub>4<\/jats:sub>\u2010promoted hepatocarcinogenesis in male Wistar rats was manifested biochemically by elevation of serum hepatic tumor markers tested; \u03b1\u2010fetoprotein and carcinoembryonic antigen. In addition, hepatocarcinogenesis was further confirmed by a significant increase in hepatic tissue growth factors; vascular endothelial growth factor, basic fibroblast growth factor, and hydroxyproline content. A marked decrease in endostatin and metallothonein were also observed. Long\u2010term ginger extract administration 2 weeks before induction of hepatocarcinogenesis and throughout the experimental period prevented the decrease of the hepatic content of metallothionein and endostatin and the increase in the growth factors induced by the carcinogen. Moreover, ginger extract normalize serum hepatic tumor markers. Histopathological examination of liver tissue also correlated with the biochemical observations. These findings suggest a protective effect of ginger extract against premalignant stages of liver cancer in the DEN\u2010initiated and CCl<jats:sub>4<\/jats:sub>\u2010promoted hepatocarcinogenesis model in rats.<\/jats:p>","DOI":"10.1002\/biof.122","type":"journal-article","created":{"date-parts":[[2010,9,24]],"date-time":"2010-09-24T12:58:26Z","timestamp":1285333106000},"page":"483-490","source":"Crossref","is-referenced-by-count":28,"title":["Ginger ingredients inhibit the development of diethylnitrosoamine induced premalignant phenotype in rat chemical hepatocarcinogenesis model"],"prefix":"10.1002","volume":"36","author":[{"given":"Mahmoud A.","family":"Mansour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh A.","family":"Bekheet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim S.","family":"Al\u2010Rejaie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Othman A.","family":"Al\u2010Shabanah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawfeq A.","family":"Al\u2010Howiriny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammar C.","family":"Al\u2010Rikabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman A.","family":"Abdo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,9,24]]},"reference":[{"key":"e_1_2_7_2_2","first-page":"4217","article-title":"The multistep nature of cancer development","volume":"44","author":"Farber E.","year":"1984","journal-title":"Cancer Res."},{"key":"e_1_2_7_3_2","first-page":"903","article-title":"Hepatocellular carcinoma","volume":"47","author":"Lemoine A.","year":"1999","journal-title":"Pathol. 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