PERTURBATION OF CELL-CYCLE KINETICS IN THE MAMMARY-GLAND BY STILBENE ESTROGEN, DIETHYLSTILBESTROL (DES)

In the present study we have examined the effect of stilbene estrogen on the proliferative activity, cell cycle kinetics and the differentiation of the mammary gland of female Noble rats. The exposure of animals to stilbene estrogen (diethylstilbestrol) or natural estrogen (estrone) (10 mu g/24 h) significantly increased proliferation in mammary epithelial cells. Both labeling index and growth fraction were increased by DES or estrone treatment. In addition, both stilbene and natural estrogen exposure altered cell cycle kinetics. Stilbene estrogen exposure to animals increased the conversion of mammary epithelial cells from G0 to G1 and G1 to S-phase cells by 8.3- and 8.5-fold, respectively, compared to that of control. Differentiation measured by the degree of lobular maturation revealed that the conversion of immature structures to mature structures was significantly increased by 2.4-fold in response to DES or estrone exposure compared to that of control. Perturbation of cell cycle is considered as a risk factor for the development of cancer. Changes in proliferation and cell cycle have been shown to lead to genetic instability, ultimately resulting in cell transformation, Our results indicated an increase in labeling index and growth fraction and a perturbation in cell cycle kinetics from DES or estrone exposure. Perturbation of cell cycle in response to stilbene estrogen exposure may produce adverse effects in the mammary glands of the Noble rats.