TRANSLATE

Genotoxicity of estrogens

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.

Induction of micronuclei, DNA strand breaks and HPRT mutations in cultured Chinese hamster V79 cells by the phytoestrogen coumoestrol.

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.