Aryl hydrocarbon receptor-based antiestrogens as treatments for breast cancer /
Breast cancer is a leading cause of premature death of women and lifetime exposure to unopposed estrogens (E2) has been established as a risk factor for breast cancer. It has been suggested that hydroxylated metabolites of E2 may be important in mammary carcinogenesis, and that exposure to certain...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
2000.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=727726331&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Breast cancer is a leading cause of premature death of women and lifetime exposure to unopposed estrogens (E2) has been established as a risk factor for breast cancer. It has been suggested that hydroxylated metabolites of E2 may be important in mammary carcinogenesis, and that exposure to certain environmental contaminants might increase estrogen metabolism and thereby contribute to breast cancer. Studies presented in this dissertation have investigated a proposed bioassay to identify mammary carcinogens based on their ability to affect P450-mediated metabolism of E2 in MCF-7 human breast cancer cells, and it is concluded that chemical-induced increases in the E2 16α-/2-hydroxyestrone ratios of MCF-7 human breast cancer cells do not predict mammary carcinogens. The mito- genicity of E2 and four hydroxy-metabolites is also investigated. The majority of early stage mammary tumors express the estrogen receptor (ER) and respond to endocrine therapy such as tamoxifen (TAM) while later stage and TAM-resistant tumors tend to be ER negative and require more aggressive treatment with cytotoxic antineoplastic drugs. New ER antagonists and ligands for other receptors including the retinoic acid receptor, the peroxisome proliferator-activated receptor, the vitamin D receptor and the aryl hydrocarbon receptor (AhR), are being developed for their antiestrogenic and antitumorigenic potential. Studies in this dissertation have demonstrated the potent activity of two classes of relatively nontoxic selective AhR modulators (SAhRMs) represented by 6-methyl-13,8- trichlorodibenzofuran and diindolylmethane, to inhibit growth of carcinogen-induced mammary tumors in rats and proliferation of human breast cancer cell lines in vitro and in athymic nude mouse xenograft experiments. |
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| Item Description: | Vita. "Major Subject: Toxicology". |
| Physical Description: | xiv, 322 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 215-321). |