Survival and phase sensitivity of HeLa cells treated with dianhydrogalactitol (NSC-132313)

The effect of dianhydrogalactitol on survival and phase sensitivity of the cell cycle of HeLa cells was studied. In survival experiments no cells survived when the drug was added and left in contact with the cells at or above a dose of 0.7 mug/ml. Cells synchronized by the mitotic-selection method showed changing sensitivity to the drug during the cell cycle. G, late-S, and M phases were more sensitive to dianhydrogalactitol than the early-S and G phases. The DNA synthetic phase was divided into an early low sensitive and a late highly sensitive stage. The different sensitivity of mid-G and early-S phases was further established in separate survival experiments. Cells treated in G phase entered M phase in a manner similar to untreated control cells, while the progress of cells in S or G phase during treatment was delayed significantly. Lack of phase specificity of this drug is consistent with that of other alkylating agents. Changing sensitivity during some phases of the cell cycle proves that some metabolic events are especially sensitive to this particular drug.