Journal Article

Vitamin C and α-naphthoflavone prevent estrogen-induced mammary tumors and decrease oxidative stress in female ACI rats

Sarah M. Mense, Bhupendra Singh, Fabrizio Remotti, Xinhua Liu and Hari K. Bhat

in Carcinogenesis

Volume 30, issue 7, pages 1202-1208
Published in print July 2009 | ISSN: 0143-3334
Published online April 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp093
Vitamin C and α-naphthoflavone prevent estrogen-induced mammary tumors and decrease oxidative stress in female ACI rats

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

The mechanisms underlying the pathogenesis of estrogen-induced breast carcinogenesis remain unclear. The present study investigated the roles of estrogen metabolism and oxidative stress in estrogen-mediated mammary carcinogenesis in vivo. Female August Copenhagen Irish (ACI) rats were treated with 17β-estradiol (E2), the antioxidant vitamin C, the estrogen metabolic inhibitor α-naphthoflavone (ANF), or cotreated with E2 + vitamin C or E2 + ANF for up to 8 months. E2 (3 mg) was administered as an subcutaneous implant, ANF was given via diet (0.2%) and vitamin C (1%) was added to drinking water. At necropsy, breast tumor incidence in the E2, E2 + vitamin C and E2 + ANF groups was 82, 29 and 0%, respectively. Vitamin C and ANF attenuated E2-induced alterations in oxidative stress markers in breast tissue, including 8-iso-prostane F formation and changes in the activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase. Quantification of 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2) formation in breast tissue confirmed that ANF inhibited 4-hydroxylation of E2 and decreased formation of the highly carcinogenic 4-OHE2. These results demonstrate that antioxidant vitamin C reduces the incidence of estrogen-induced mammary tumors, increases tumor latency and decreases oxidative stress in vivo. Further, our data indicate that ANF completely abrogates breast cancer development in ACI rats. The present study is the first to demonstrate the inhibition of breast carcinogenesis by antioxidant vitamin C or the estrogen metabolic inhibitor ANF in an animal model of estrogen-induced mammary carcinogenesis. Taken together, these results suggest that E2 metabolism and oxidant stress are critically involved in estrogen-induced breast carcinogenesis.

Journal Article.  5464 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.