Dose-Dependent Effect of 17β-Estradiol Determined by Growth Curves and Flow Cytometric DNA Analysis of a Human Breast Carcinoma (T61) Grown in Nude Mice

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Abstract
An estrogen and progesterone receptor-positive human breast carcinoma (T61) grown in nude mice was exposed to 1.0, 0.1, 0.01, and 0.001 mg 17β-estradiol. These doses resulted in serum peak concentrations (day 1) of estradiol ranging from 3.5 × 10-8 to 6.9 × 10-10M. The effect of the treatment was evaluated using growth curves and flow cytometric DNA analysis. The treatment induced a dose-dependent growth delay and dose-dependent changes in the cell cycle distribution. The cell cycle changes comprised a decrease in the G1 phase, an accumulation of cells in the S phase, and an increasing fraction of polyploid cells. The results suggest that estradiol induces a dose-dependent cell killing effect in the T61 human breast carcinoma. The correlation between the treatment-induced growth delay and the effect on the cell cycle distribution indicates that the changes in the cell cycle are a reflection of the estradiol-induced cell destruction. Since no tumor growth stimulation could be observed even at very low serum estradiol concentrations, the T61 human breast carcinoma may represent a new aspect in the study of human breast cancer.