Mechanistic studies of xenobiotic and natural compounds that modulate estrogen-receptor and aryl-hydrocarbon receptor signaling pathways /
The most common cancers in women occur in hormonally-responsive tissues including breast and endometrium and have been associated with prolonged exposure to estrogens (E2). Anthropogenic and natural compounds exhibit a broad range of estrogenic and antiestrogenic activities that may influence breast...
| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
[Place of publication not identified] :
[publisher not identified] ;
2000.
|
| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=731990091&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | The most common cancers in women occur in hormonally-responsive tissues including breast and endometrium and have been associated with prolonged exposure to estrogens (E2). Anthropogenic and natural compounds exhibit a broad range of estrogenic and antiestrogenic activities that may influence breast cancer. CYP1A2 is a major inducible cytochrome P450 isozyme in humans and plays an important role in mediating carcinogenesis. However, regulation of CYP1A2 gene expression is not clearly understood. This study has demonstrated strain- and age-dependent induction of CYP1A2 gene expression in genetically inbred mice. Endogenous estrogens can be hydrogenated at multiple positions by cytochrome P450 enzymes and CYP1A2 plays a major role in hepatic 2-hydroxylation of E2. Studies have indicated that E2-metabolites may play an important role in development of breast cancer. Studies in this dissertation have investigated the comparative mutagenicity of E2 and four hydroxy-metabolites in human breast cancer cells. Antiestrogen therapy with tamoxifen is widely used for treatment of breast cancer. However, the efficacy of this drug for estrogen-receptor negative tumors is much lower. Studies in this dissertation have characterized antiestrogenic activities of non-toxic aryl-hydrocarbon receptor agonists such as diindolylmethane analogs as well as a series of hetero-aromatic compounds which inhibit E2-mediated responses in human breast cancer cells and may develop into drugs for treatment human breast cancer. The antiestrogenic activity of anthropogenic compounds such as coplanar PCBs was also characterized in this dissertation. |
|---|---|
| Item Description: | Vita. "Major Subject: Toxicology". |
| Physical Description: | xiii, 197 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 162-196). |