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Title: INHIBITION OF RAT MAMMARY TUMORIGENESIS BY CONCORD GRAPE JUICE CONSTITUENTS

Author
item SINGLETARY, KEITH - U. OF IL-URBANA-CHAMPAIGN
item STANSBURY, MATTHEW - U. OF IL-URBANA-CHAMPAIGN
item GIUSTI, MONICA - UNIV. OF MARYLAND
item VAN BREEMAN, RICHARD - UNIV. OF IL-CHICAGO
item WALLIG, MATTHEW - U. OF IL-URBANA-CHAMPAIGN
item Rimando, Agnes

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/12/2003
Publication Date: 11/1/2003
Citation: Singletary, K.W., Stansbury, M.J., Giusti, M., Van Breeman, R.B., Wallig, M.A., Rimando, A.M. 2003. Inhibition of rat mammary tumorigenesis by Concord grape juice constituents. Journal of Agricultural and Food Chemistry. 51:7280-7286.

Interpretive Summary: The effects of Concord grape juice phenolic constituents on the promotion of chemically-induced rat mammary tumor development and on the proliferation of a rat mammary adenocarcinoma cell line were studied. Grape juice formulations incorporated in the drinking fluid of rats significantly inhibited mammary adenocarcinoma compared to controls. Final tumor mass also was significantly decreased for animals provided the grape juice compared to controls. In addition, DNA synthesis of the rat mammary adenocarcinoma cell line was significantly inhibited for cells treated with a grape extract. These studies thus indicate that Concord grape juice phenolic constituents can inhibit the promotion stage of chemically-induced rat mammary tumorigenesis, in part by suppressing cell proliferation.

Technical Abstract: The effects of Concord grape juice constituents on the promotion of chemically-induced rat mammary tumor development and on the proliferation of a rat mammary adenocarcinoma cell line were studied. Isocaloric grape juice formulations provided in the drinking fluid of rats at concentrations of 489 and 651 mg phenolics/dL of fluid significantly inhibited mammary adenocarcinoma multiplicity compared to controls. Final tumor mass also was significantly decreased for animals provided these two grape juice concentrations, compared to controls. In addition, DNA synthesis of the rat mammary adenocarcinoma RBA cell line was significantly inhibited in a dose-dependent manner for cells treated with a grape extract, with an IC50 dose of ~14 µg phenolics/ml. This inhibition of DNA synthesis was not accompanied by changes in 8-oxo-deoxyguanosine formation, but was associated with a modest (165) and significant cell cycle arrest at the G1 phase. These studies thus indicate that Concord grape juice constituents can inhibit the promotion stage of DMBA-induced rat mammary tumorigenesis, in part by suppressing cell proliferation.