EFFECTS OF TAMOXIFEN ON ESTROGEN-INDUCED ENHANCEMENT OR INHIBITION OF TUMOR-GROWTH IN MOUSE LEYDIG-CELL TUMOR LINES

Abstract

To avoid the complex dual effects of estrogen (E) and antiestrogen, an attempt was made to establish the tumor lines in which estrogens show either stimulatory or inhibitory property in terms of the tumor growth. The administration of E to host mice bearing 1 of the mouse Leydig cell tumor lines, called T 124958-R, resulted in marked enhancement of the tumor growth even at pharmacological levels of E. On the other hand, estrogenization of host mice almost completely inhibited the growth of the other tumor line (T 22137) without detectable stimulatory effects. The physicochemical properties of the cytosol E receptor in both sublines were found to be similar in relation to the affinity toward ligands, steroid specificity, sedimentation profile and the dissociation rate kinetics. Using these tumor lines, the action mechanism of tamoxifen on the tumor growth was examined. Daily administration of this compound (30 .mu.g/mouse) led to enhanced tumor growth in T 124958-R, while the growth of T 22137 was inhibited by the same procedure. In the combination experiments, tamoxifen was found to be unable to antagonize E-induced enhancement or inhibition of the growth in these tumors. In addition, both tumors contained similar levels of the antiestrogen binding sites. Tamoxifen evidently modulated the tumor growth through its estrogenic potency.