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- Metzler M, Kulling SE,
Pfeiffer E and Jacobs E. Z Lebensm Unters Forsch A 1998,
206: 367-73.
- 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.
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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- Kulling SE, Metzler M.
Food Chem Toxicol 1996, 35:605-13.
- 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 on the clastogenicity and mutagenicity
of COUM in mammalian cells.
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