Carcinogenesis Advance Access published online on October 24, 2003
Carcinogenesis, doi:10.1093/carcin/bgg198
© 2003 by Oxford University Press
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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1 Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL 61801
* Corresponding author. E-mail: helferic{at}uiuc.edu.
Received 27 June 2003
; revised 11 September 2003
; accepted 12 October 2003
Due to the estrogenic properties of soy derived isoflavones, many postmenopausal women are using these compounds as a natural alternative to hormone replacement therapy (HRT). How isoflavones impact breast cancer in postmenopausal women is important, because a majority of breast cancer cases occur in this age group. Chemical induction of mammary tumors in female rats has been used to determine that exposure of the mammary gland to soy isoflavones prior to tumor induction is protective against tumor formation. Here we investigate the effect of dietary genistein on mammary tumors that have already formed. The study was designed to determine the action of dietary genistein in a low endogenous estrogen environment as is observed in postmenopausal women. Animals were ovariectomized (OVX) after mammary tumor development and were then placed into one of three treatment groups: positive-control (OVX+ estradiol implant), genistein (OVX+ dietary genistein), and negative-control (OVX alone). Tumors were distinguished as malignant or benign by histopathological examination and were further characterized as either estrogen-dependent or independent using immunohistochemistry to identify the presence of both estrogen receptor alpha (ER
genistein, breast cancer, phytoestrogen
Dietary genistein results in larger MNU-induced, estrogen-dependent mammary tumors following ovariectomy of sprague-dawley rats
2 National Center for Toxicological Research, Jefferson, AR 72079
3 Department of Veterinary Biosciences, University of Illinois, Urbana IL 61802
4 Department of Psychology, University of Illinois, Urbana IL 61820
5 Department of Veterinary Pathobiology, University of Illinois, Urbana, IL 61802
) and the progesterone receptor (PR). Genistein at 750 ppm increased the weight of estrogen-dependent adenocarcinomas in ovariectomized rats compared to the negative-control animals. Genistein treatment also resulted in a higher percentage of proliferative cells in tumors and increased uterine weights when compared to negative-control animals. Collectively, these effects are likely due to the estrogenic activity of genistein. Plasma genistein concentrations in animals fed the isoflavone-containing diet were at physiological levels relevant to human exposure. Estradiol concentrations in ovariectomized animals not receiving an estradiol supplement were similar to those observed in postmenopausal women. These data suggest that in an endogenous estrogen environment similar to that of a postmenopausal woman, dietary genistein can stimulate the growth of chemically induced estrogen-dependent mammary tumors.
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