Perturbed cell kinetics of 9L rat brain tumor cells following dianhydrogalactitol.

Kinetic changes induced by dianhydrogalactitol (DAG) in cultured 9L rat brain tumor cells were studied using conventional autoradiography and flow cytometry. Cell cycle parameters for the untreated cell line were: G1, 8.5 hours; S, 8.2 hours; G2, 3.2 hours; M, 0.5 hour; and cell cycle time, 19.5--20 hours. Treatment with 5 micrograms/ml of DAG, which caused 89.8% cell kill as measured by the colony-forming efficiency assay, resulted in the following effects: (a) undisturbed progression of G2 cells toward mitosis; (b) disturbed progression of the cells in the S--G2 boundary; (c) extreme prolongation of DNA synthesis time; and (d) temporary accumulation in G2 phase of cells that were in G1 or S phase at the time of treatment.