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Title: Antioxidant butylated hydroxyanisole inhibits estrogen-induced breast carcinogenesis in female ACI rats.

Authors: Singh, Bhupendra; Mense, Sarah M; Remotti, Fabrizio; Liu, Xinhua; Bhat, Hari K

Published In J Biochem Mol Toxicol, (2009 May-Jun)

Abstract: Exposure to estrogens is suggested to be a risk factor in human breast cancer development. The mechanisms underlying estrogen-induced cancer have not been fully elucidated. Both estrogen receptor (ER)-mediated proliferative processes and ER-independent generation of oxidative stress are suggested to play important roles in estrogen-induced breast carcinogenesis. In the current study, we investigated the role of oxidative stress in breast carcinogenesis using the ACI rat model of mammary tumorigenesis. Female ACI rats were treated with 17beta-estradiol (E(2)), butylated hydroxyanisole (BHA), or a combination of E(2) + BHA for up to 240 days. Cotreatment of rats with E(2) + BHA reduced estrogen-induced breast tumor development with tumor incidence of 24%, a significant decrease relative to E(2) where tumor incidence was 82%. Proliferative changes in the breast tissue of E(2) + BHA-treated animals were similar to those observed in E(2)-treated animals. Tissue levels of 8-isoprostane, a marker of oxidant stress, as well as the activities of antioxidant enzymes including glutathione peroxidase, superoxide dismutase, and catalase were quantified in the breast tissues of rats treated with E(2) + BHA and compared to activity levels found in E(2)-treated animals and respective age-matched controls. Cotreatment with BHA inhibited E(2)-mediated increases in 8-isoprostane levels as well as activities of antioxidant enzymes. In summary, these data suggest that estrogen-mediated oxidant stress plays a critical role in the development of estrogen-dependent breast cancers and BHA inhibits E(2)-dependent breast carcinogenesis by decreasing oxidant stress.

PubMed ID: 19526586 Exiting the NIEHS site

MeSH Terms: Animals; Antioxidants/metabolism*; Antioxidants/pharmacology*; Breast Neoplasms/chemically induced; Breast Neoplasms/drug therapy; Breast Neoplasms/metabolism; Butylated Hydroxyanisole/pharmacology*; Dinoprost/analogs & derivatives; Dinoprost/metabolism; Estradiol/adverse effects*; Estradiol/pharmacology; Estrogens/adverse effects*; Estrogens/pharmacology; Female; Humans; Mammary Neoplasms, Experimental/chemically induced; Mammary Neoplasms, Experimental/drug therapy*; Mammary Neoplasms, Experimental/metabolism; Oxidative Stress/drug effects; Rats; Rats, Inbred ACI

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