Because of the structural resemblance to the female hormone, phytoestrogen is another important class of endocrine disruptor. In the present project, we evaluated the effects of phytoestrogens isoliquiritigenin (ILN), hesperetin (HES), genistein, (GEN) and naringenin (NAR) on estrogen metabolism and also their effects on MCF-7 tumor growth in ovariectomized nude mice. We found that these phytoestrogens had differential effect on MCF-7 xenografts. NAR and GEN had totally different responses in the tumor growth. In contrast, ILN and HES only deterred MCF-7 xenograft growth when CYP19 was overexpressed in the graft. / Breast cancer is one of the most prevalent female cancers in Hong Kong and western countries. Prolonged exposure to estrogen has been associated with increased risk of breast cancer. Many enzymes are responsible for estrogen metabolism, for instance, aromatase (CYP19) is responsible for biosynthesis; CYP1 family enzymes hydroxylate estrogen; COMT (catechol-O-methyltransferase) inactivates the hydroxyestrogen; and UDP-glucuronosyltransferase 1A1 (UGT1A1) eliminates the estrogen metabolites. In this project, we employed cell and animal models to address estrogen metabolism-related questions under the influence of endocrine disruptors. / TCDD is a prototype compound of a whole class of halogenated aromatic hydrocarbons termed dioxin-like contaminants, which are also known to be endocrine disruptors. Because of their persistence in the environment dioxins are one of the most concerned classes of carcinogens. Humans can be exposed to this pollutant through contaminated food, air, drinking water, etc. We found that pre-ovariectomy administration of TCDD could significantly reduce aromatase expression in the brain but increase the expression in the adipose tissue. Our results suggested that the timing of exposure to the toxicant could determine the estrogenicity of TCDD. / The present project indicated that endocrine disruptors can alter the metabolism of estrogen; however, the significance of this alteration may be specific to tissues' phenotype and the timing of exposure. / Ye Lan. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 169-192). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344609 |
| Date | January 2009 |
| Contributors | Ye, Lan, Chinese University of Hong Kong Graduate School. Division of Life Sciences. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (x, 192 leaves : ill.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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