Growth inhibitory effect of 4-hydroxy-tamoxifen on the BT-20 mammary cancer cell line.

The antiestrogenic activities of Tamoxifen have been well documented and this molecule has been successfully used in the treatment of hormone dependent breast cancer. In the present experiments we demonstrate that 4-hydroxy-Tamoxifen (OH-TAM) is able to reduce the growth of the BT-20 cell line which is devoid of estrogen and progesterone receptors. Various parameters have been investigated in growth studies under control conditions and in the presence of OH-TAM. Cell numerations, [3H]thymidine incorporation per cell or per microgram of DNA have shown that OH-TAM reduces the growth rate in proportion to its concentration from 10(-9) M to 10(-6) M. This activity is not reversed by estradiol addition. It is unaffected by the presence or the absence of Phenol Red in the medium. Analysis by flow cytometry suggests that it takes place before the S phase of the cycle. Examination of control and treated cells by Electron Microscopy shows no sign of toxicity. The growth inhibitory activity of OH-TAM on these cell lines appears therefore unrelated to its antiestrogenic properties.