Response of cultured human glioblastomas to radiation and BCNU chemotherapy.

Abstract

✓Individual and combined effects of ionizing radiation and chemotherapy with 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) on glial tumor cells were assessed in cultures derived from human glioblastomas. Drug and radiation exposures were performed on cell monolayers in 0.02 ml wells of microtest plates. Response to treatment was determined from serial observations on surviving populations in the original wells and comparisons with matched control cultures. Chemosensitivity was more variable than radiosensitivity in cell lines derived from five different glioblastomas: BCNU caused growth inhibition of 4% to 85% in doses of 8 µg/ml for 3 days compared to a 40% to 73% reduction after 400 rads of radiation. These findings were all significant statistically. Single doses above 600 to 800 rads appeared lethal, causing widespread loss of cells or transformation into giant forms that did not multiply. The doseresponse curves after BCNU and radiation treatment of cultured glial tumor cells were exponential, demonstrating that both modalities affected a constant fraction of the exposed cell populations according to dose. The observations on radiosensitivity of human glial tumor cells conformed to the generally known responses of cultured normal and neoplastic mammalian cells to ionizing radiation. BCNU in the higher doses tested acted as a possible radiosensitizing agent to potentiate the lethal effects of radiation since an increased rate of cell loss was demonstrated in glioma cultures exposed to this drug and radiation compared to those treated only by irradiation. These results in a controlled experimental environment support the concept that a combination of BCNU and radiation therapy should increase the time of survival of patients with malignant gliomas.