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- Do phytoestrogens prevent cancer? The evidence to support
the industry claim is scant and recent work indicates that phytoestrogens
may actually increase the risk of breast cancer.
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- HOT OFF THE PRESS is an article from Japan in which
the author proposes a link between the soy phytoestrogen genistein and
infantile leukemia.
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- Infantile Leukemia And Soybeans - A Hypothesis
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- Leukemia 1999, 13:317-20
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- Abstract: Recent molecular-genetic studies have revealed
that in the majority of patients with secondary leukemia induced by topoisomerase
II (topo II) inhibitors and also with infantile acute leukemia (IAL),
the breakpoints are clustered within scaffold attachment regions (SARs)
of 3'-MLL-bcr near exon 9. Genistein, abundant in soybeans, is reported
to be a potent nonintercalative topo II inhibitor. It interferes with
the break-reseal reaction of topo II by stabilizing a cleavable complex,
which in the presence of detergents, results in DNA strand breaks. The
present study revealed that genistein induced chromatid-type aberrations,
in which chromatid exchanges are often observed. Genistein seems to act
in a manner very similar to that of VP-16, although the latter is reported
to produce both chromatid- and chromosome-type aberrations. In view of
this pharmacological similarity between genistein and VP-16, and also
the similarity of breakpoint clustering regions within the MLL gene in
reported cases with secondary leukemia and IAL, genistein may be largely
responsible for the development of IAL.
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- Earlier work by Manfred Metzler has already shown that
genistein is a potential clastogen; Metzler's work has been reported in
the following articles"
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- Genotoxicity Of Estrogens.
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- By Metzler M, Kulling SE, Pfeiffer E and Jacobs E. Z
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- Lebensm Unters Forsch A 1998, 206: 367-73.
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- Abstract: Genotoxic effects of the endogenous mammalian
estrogen 17-beta-estradiol and the synthetic estrogen diethylstilbestrol
have recently been demonstrated, e.g. the induction of numerical chromosome
aberrations (aneuploidy, i.e. the condition in which on or more whole
chromosomes of a normal set are missing or present in more than the usual
(set of copies) and the formation of deoxyribonucleic acid (DNA) adducts.
It is likely that the genotoxicity of the estrogens acts in concert with
their hormonal activity to give rise to carcinogenic effects.
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- Many of the phytoestrogens that occur in plants and
the numerous anthropogenic estrogens in our environment, which are ingested
in food, have not yet been examined for their genotoxic potential. Recent
studies have demonstrated that some but not all of these estrogens exhibit
genotoxicity. The type and strength of the genotoxicity strongly depends
on the chemical structure and does not correlate with estrogenicity.
For example, coumestrol and genistein are clastogenic in cultured mammalian
cells and lead to gene mutations, whereas biochanin-A and bisphenol-A
have the potential to aneuploidy. Daidzein, enterolactone, enterodiol
and certain bisphenols are devoid of genotoxic effects. The genotoxicity
should be determined individually for each estrogen and taken into account
in the assessment of carcinogenic risk.
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- Induction of micronuclei, DNA strand breaks and HPRT
mutations in cultured Chinese hamster V79 cells by the phytoestrogen coumoestrol.
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- By Kulling SE, Metzler M.
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- Food Chemical Toxicology 1996, 35:605-13.
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- Abstract: Coumoestrol (COUM), genistein (GEN) and daidzein
(DAI) are major phytoestrogens present in numerous plants eaten by humans
and food-producing animals. Little is known about the genotoxicity of
these natural compounds. The effects of COUM, GEN and DAI were studied
in cultured Chinese hamster V79 cells at various endpoints. None of the
substances affected the cytoplasmic microtubule complex or the mitotic
spindle. However, COUM and GEN but not DAI proved to be strong inducers
of DNA strand breaks and micronuclei containing acentric fragments, as
shown with antikinetochore antibodies. The clastogenicity of GEN may be
due to its non-intercalative inhibitory effect on topoisomerase II, whereas
COUM may act through topoisomerase II inhibition and/or DNA intercalation.
COUM was also a clear inducer of hypoxanthine guanine phosphoribosyltransferase
(HPRT) mutations in V79 cells; GEN was only marginally active and DAI
inactive at this endpoint. This is the first report n the clastogenicity
and mutagenicity of COUM in mammalian cells.
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- And here's what some other experts say about phytoestrogens
and cancer:
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- Postmenopausal women consuming soy isoflavones as a
natural HRT may place themselves at greater risk of breast cancer. In 1996
Dr Nicholas Petrakis, University of California, San Francisco, reported
that 'Prolonged consumption of soy protein isolate has a stimulatory effect
on the premenopausal female breast, characterised by increased secretion
of breast fluid, the appearance of hyperplastic epithelial cells and elevated
levels of estradiol. These findings are suggestive of an estrogenic stimulus
from the isoflavones genistein and daidzein contained in soy protein isolate'
(Petrakis NL et al. Stimulatory influence of soy protein isolate on breast
secretion in pre- and postmenopausal women. Cancer Epid Bio Prev 1996;
5: 785-794).
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- In support of a cautionary approach to consuming soy
to prevent breast cancer is Dr Bill Helferich of the University of Illinois.
He has recently stated that 'there is potential for dietary genistein
to stimulate the growth of estrogen-dependent tumors in humans with low
circulating endogenous estrogen levels, such as those found in postmenopausal
women'. Read it for yourself!
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- Estrogenic effects of genistein on the growth of estrogen
receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo.
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- By Hsieh CY, Santell RC, Haslam SZ, Helferich WG.
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- Cancer Research 1998 Sep 1 58:17 3833-8
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- Abstract: Genistein, found in soy products, is a phytochemical
with several biological activities. In the current study,our research
focused on the estrogenic and proliferation-inducing activity of genistein.
We have demonstrated that genistein enhanced the proliferation of estrogen-dependent
human breast cancer (MCF-7) cells in vitro at concentrations as low as
10 nM, with a concentration of 100 nM achieving proliferative effects
similar to those of 1 nM estradiol. Expression of the estrogen-responsive
gene pS2 was also induced in MCF-7 cells in response to treatment with
a concentration of genistein as low as 1 microM. At higher concentrations
(above 20 microM), genistein inhibits MCF-7 cell growth. In vivo, we
have shown that dietary treatment with genistein (750 ppm) for 5 days
enhanced mammary gland growth in 28-day-old ovariectomized athymic mice,
indicating that genistein acts as an estrogen in normal mammary tissue.
To evaluate whether the estrogenic effects observed in vitro with MCF-7
cells could be reproduced in vivo, MCF-7 cells were implanted s.c. in ovariectomized
athymic mice, and the growth of the estrogen-dependent tumors was measured
weekly. Negative control animals received the American Institute of Nutrition
(AIN)-93G diet, the positive control group received a new s.c. estradiol
(2 mg) pellet plus the AIN-93G diet, and the third group received genistein
at 750 ppm in the AIN-93G diet. Tumors were larger in the genistein (750
ppm)-treated group than they were in the negative control group, demonstrating
that dietary genistein was able to enhance the growth of MCF-7 cell tumors
in vivo. Increased uterine weights were also observed in the genistein-treated
groups. In summary, genistein can act as an estrogen agonist in vivo and
in vitro, resulting in the proliferation of cultured human breast cancer
cells (MCF-7) and the induction of pS2 gene expression. Here we present
new information that dietary genistein stimulates mammary gland growth
and enhances the growth of MCF-7 cell tumors in ovariectomized athymic
mice. Dr Craig Dees of Oak Ridge National Laboratory has also found
that soy isoflavones cause breast cancer cells to grow. He reported that
'low concentrations of genistein may stimulate MC-7 cells to enter the
cell cycle'. Dees concluded that ' women should not consume particular
foods (eg. soy-derived products) to prevent breast cancer'.
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- Dietary estrogens stimulate human breast cells to enter
the cell cycle.
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- By Dees C, Foster JS, Ahamed S, Wimalasena J.
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- Environmental Health Perspective 1997 Apr 105 Suppl 3
633-6
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- 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 ICI182,780 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.
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- By Ardies CM and Dees C.
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- Medical Hypotheses 1998 Jun 50:6 457-64
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- 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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- Why does unfermented soy causes problems?
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