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- Dietary estrogens stimulate human breast cells to
enter the cell cycle.
- Dees C, Foster JS, Ahamed S, Wimalasena J. Environ
Health Perspect 1997 Apr 105 Suppl 3 633-6
- Abstract
- It has been suggested that dietary estrogens neutralize the
effect of synthetic chemicals that mimic the effects of estrogen (i.e., xenoestrogens,
environmental estrogens). Genistein, a dietary estrogen, inhibits the growth of breast
cancer cells at high doses but additional studies have suggested that at low doses,
genistein stimulates proliferation of breast cancer cells. Therefore, if dietary estrogens
are estrogenic at low doses, one would predict that they stimulate estrogen-receptor
positive breast cancer cells to enter the cell cycle. Genistein and the fungal toxin
zearalenone were found to increase the activity of cyclin dependent kinase 2 (Cdk2) and
cyclin D1 synthesis and stimulate the hyperphosphorylation of the retinoblastoma
susceptibility gene product pRb105 in MCF-7 cells. The steroidal antiestrogen ICI 182,780
suppressed dietary estrogen-mediated activation of Cdk2. Dietary estrogens not only failed
to suppress DDT-induced Cdk2 activity, but were found to slightly increase enzyme
activity. Both zearalenone and genistein were found to stimulate the expression of a
luciferase reporter gene under the control of an estrogen response element in MVLN cells.
Our findings are consistent with a conclusion that dietary estrogens at low concentrations
do not act as antiestrogens, but act like DDT and estradiol to stimulate human breast
cancer cells to enter the cell cycle.
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- Xenoestrogens significantly enhance risk for
breast cancer during growth and adolescence.
- Ardies CM and Dees C. Med Hypotheses 1998 Jun 50:6 457-64
- Abstract
- Breast cancer is one of the most common forms of cancer
observed in women, and endogenous estrogen is thought to play a major role in its
development. Because of this, any conditions or exposures which enhance estrogenic
responses would result in an increased risk for breast cancer. The role of xenoestrogenic
compounds, such as DDT, in the etiology of breast cancer is still very controversial. In
the following paper we discuss recently-published observations by ourselves and others
which indicate that xenoestrogens may play a significant role in the development of breast
cancer. Specifically, we hypothesize that during periods of high growth rates and during
breast development the sensitivity of breast cells to estrogenic compounds is sufficiently
great for xenoestrogens to significantly enhance risk for breast cancer.
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- Author Address
- Health Sciences Research Division, Oak Ridge National
Laboratory, Tennessee, USA.
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