Cytotoxic effects of 1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) on cultured human glioblastomas.

Two cultured human glioblastoma cell lines were exposed to graded doses of BCNU, and the sequential cytoxic and cytocidal changes were studied histologically. Changes included cessation of mitotic activity, reduction in population, rounding and clumping of the cells, nuclear pyknosis, and cell death. The intensity of the changes was proportional to the dosage. With 3 daily doses of 18 mug/ml, the population in Tumor A-172 was only 20% of that in the controls, and 75% of the cells present appeared conviable. This dosage is about four times that used in a single course in treating humans. After 3 doses at 60 mug/ml, cell death appeared complete, but transfer without additional treatment brought out 2-min foci of viable cells, with several mitoses. A more anaplastic glioblastoma, T98, was much less sensitive to BCNU, responding only by lowered population density, decreased mitoses and slight-to-moderate cytotoxicity in one experiment.