GENOTOXICITY OF ESTROGENS

Genotoxic effects of the endogenous mammalian estrogen 17 beta-estradi ol and the synthetic estrogen diethylstilbestrol have recently been de monstrated, e.g. the induction of numerical chromosome aberrations (an euploidy, i.e., the condition in which one or more whole chromosomes o f a normal set are missing or present in more than the usual set of co pies) and the formation of deoxyribonucleic acid (DNA) adducts. It is likely that the genotoxicity of the estrogens acts in concert with the ir hormonal activity to give rise to their carcinogenic effects. Many of the phytoestrogens that occur in plants and the numerous anthropoge nic estrogens in our environment, which are ingested with food, have n ot yet been examined for their genotoxic potential. Recent studies hav e demonstrated that some but not all of these estrogens exhibit genoto xicity. 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 mammalia n cells and lead to gene mutations, whereas biochanin-A and bisphenol- A have the potential to cause aneuploidy. Daidzein, enterolactone, ent erodiol and certain bisphenols are devoid of genotoxic effects. The ge notoxicity should be determined individually for each estrogen and tak en into account in the assessment of its carcinogenic risk.