RADIOSENSITIZING EFFECT OF ESTRAMUSTINE IN MALIGNANT GLIOMA IN-VITRO AND IN-VIVO

Estramustine-phosphate (EMP), a combination of nornitrogen mustard and 17 beta-estradiol, has been demonstrated to exert specific antiprolif erative effects on human glioma cells in vitro. The cytotoxic effect i s, at least partially, mediated by inhibiting microtubule function. In this study the combined effect of EMP and radiation was evaluated in the human glioma cell-lines, 251-MG and 105-MG, in vitro, and in the r at glioma BT4C in vitro and in vivo. In all cell-lines an additive eff ect of EMP and radiation was obtained in vitro. Assuming equal effect of EMP is obtained in subsequent radiation fractions, the cell kill wi ll be increased from 2-3 to 5-10 logs if delivering 30 fractions of 2 Gy combined with EMP. In the BT4C rat model the combined effect was fo und to be synergistic. Flow cytometry demonstrated an arrest in G2/M p hase in all cell-lines after EMP treatment. This block in G2/M phase i n addition to the previously demonstrated induction of free oxygen rad icals, and the increase of blood flow with an assumed subsequent incre ase of oxygenation, might provide an explanation for the observed radi osensitizing effect of estramustine.