ESTRAMUSTINE SENSITIZES HUMAN GLIOBLASTOMA CELLS TO IRRADIATION

Estramustine is an estradiol-based antimicrotubule agent that accumula tes in malignant glioma cells, resulting in a concentration-dependent inhibition of proliferation. This agent has been shown to synchronize human glioma cells at G(2)-M consistent with its known effects on the mitotic spindle and potentially could be used as a radiation enhancer. We determined the effects of estramustine on the cell cycle of gliobl astoma cells by flow cytometry. These findings were compared with clon ogenic survival in cells pretreated with varying concentrations of est ramustine prior to irradiation. These experiments indicated that 24 h treatment with 1 mu M estramustine had no effect on the percentage of G(2)-M cells and did not enhance the cytotoxic effects of radiation wh ile 10 mu M estramustine increased the G(2)M fraction by 100% associat ed with a potentiation factor as high as 8.5 and a relative radiation sensitivity at 70% cytotoxicity of 5.2 compared with 15.4 for control cells. Estramustine can be administered p.o. on a daily schedule with minimal systemic toxicity. These data suggest that estramustine may be an effective radiation enhancer for glioblastoma.