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result sql = Vitamin E down-modulates iNOS and NADPH oxidase in c-Myc/TGF-alpha transgenic mouse model of liver cancer.
Vitamin E down-modulates iNOS and NADPH oxidase in c-Myc/TGF-alpha transgenic mouse model of liver cancer.
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result sql = BACKGROUND/AIMS : Co-expression of c-Myc and TGF-alpha in the mouse liver accelerates hepatocarcinogenesis and enhances DNA damage due to chronic oxidative stress. Dietary supplementation with vitamin E (VE) inhibits hepatocarcinogenesis and reduces chromosomal alterations in the same mice. Here we investigated the sources of reactive oxygen species (ROS) production in c-Myc/TGF-alpha transgenic mice.

METHODS : Inducible nitric oxide synthase (iNOS) and NADPH oxidase levels were determined in c-Myc, TGF-alpha and c-Myc/TGF-alpha mice by RT-PCR, western blot analysis and immunohistochemistry.

RESULTS : iNOS and nitrotyrosines levels were higher in the three transgenic lines when compared with wild-type mice. Preneoplastic and neoplastic lesions from c-Myc, TGF-alpha and c-Myc/TGF-alpha transgenic mice displayed upregulation of NADPH oxidase subunits p47-, 67-phox, Rac1, HSP 70, and HO-1. Importantly, dietary supplementation with vitamin E abolished iNOS expression, lowered nitrotyrosines, p47-, p67-phox, and Rac1 levels, and suppressed HSP 70 and HO-1 proteins in c-Myc/TGF-alpha livers.

CONCLUSIONS : The results suggest that iNOS and NADPH oxidase are involved in ROS generation during c-Myc/TGF-alpha hepatocarcinogenesis and are inhibited by VE treatment. The data provide additional evidence for the potential use of VE in treatment of chronic liver diseases and HCC prevention.

Publication: J. Hepatol. 2004 Nov ;41(5)::815-22.
Publication Date: 2004 Nov
Study Author(s): Calvisi, Diego F;Ladu, Sara;Hironaka, Koji;Factor, Valentina M;Thorgeirsson, Snorri S;
Institution: Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 4146A1, 37 Convent Drive MSC 4262, Bethesda, MD 20892-4258, USA.
Shortcut link to this study:
BACKGROUND/AIMS : Co-expression of c-Myc and TGF-alpha in the mouse liver accelerates hepatocarcinogenesis and enhances DNA damage due to chronic oxidative stress. Dietary supplementation with vitamin E (VE) inhibits hepatocarcinogenesis and reduces chromosomal alterations in the same mice. Here we investigated the sources of reactive oxygen species (ROS) production in c-Myc/TGF-alpha transgenic mice.

METHODS : Inducible nitric oxide synthase (iNOS) and NADPH oxidase levels were determined in c-Myc, TGF-alpha and c-Myc/TGF-alpha mice by RT-PCR, western blot analysis and immunohistochemistry.

RESULTS : iNOS and nitrotyrosines levels were higher in the three transgenic lines when compared with wild-type mice. Preneoplastic and neoplastic lesions from c-Myc, TGF-alpha and c-Myc/TGF-alpha transgenic mice displayed upregulation of NADPH oxidase subunits p47-, 67-phox, Rac1, HSP 70, and HO-1. Importantly, dietary supplementation with vitamin E abolished iNOS expression, lowered nitrotyrosines, p47-, p67-phox, and Rac1 levels, and suppressed HSP 70 and HO-1 proteins in c-Myc/TGF-alpha livers.

CONCLUSIONS : The results suggest that iNOS and NADPH oxidase are involved in ROS generation during c-Myc/TGF-alpha hepatocarcinogenesis and are inhibited by VE treatment. The data provide additional evidence for the potential use of VE in treatment of chronic liver diseases and HCC prevention.
PMID: 15519655

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