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Evaluation of the Effects of Daidzein and Genistein (Hormone Replacement Agents) on the Genotoxic and Carcinogenic Activity of the Model Mammary Carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) in Ovarioectomized Transgenic Big Blue Rats


This project is designed to determine if hormone replacement, in this case the phytoestrogens daidzein and genistein, will alter the risk of mammary tumors.

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Rats will be exposed to a known mammary carcinogen (DMBA) and given daidzein and/or genistein. In order to model the post-menopausal human situation, the rats will be ovariectomized. </p>
In addition to the induction of tumors, other endpoints such as the ability of the DMBA to bind to DNA (DNA adduct analysis) and the frequency and types of mutations induced by DMBA will be investigated.</P>
This is an externally funded (FDA, Office of Women's Health) project. The Animal Care and Use Committee approved the project in FY 2000 and experimentation should begin in FY 2001.<br>
<li> Approximately 300 Big Blue rats will be ovariectomized and the treatment will be initiated for this study.</li>
<li> Two mutation endpoints, lacI mutation in the mammary tissue and Hprt mutation in the lymphocytes will be evaluated.</li>
<li> Animals that develop tumors (with DMBA) will be screened for mutation in p53 and H-ras genes.</li>
<li> Modulatory effect of phytoestrogens on mutation frequency spectrum as well as tumor induction and p53 and ras mutation frequency will be evaluated.</li></ol>

Aidoo, Anane
DHHS/FDA - National Center for Toxicological Research
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