Unusual Survival Kinetics of Neocarzinostatin-treated HeLa Cells: Its Relation to the Drug-inactivation

Cell survival kinetics of exponentially growing HeLa S3 cells as a function of the period of treatment with neocarzinostatin (NCS) and its relation to drug inactivation were analyzed in vitro with various concentrations of NCS, NCS activity was rapidly lost during the treatment period in a simple exponential manner with a half-life of 2 to 4 minutes depending on the treatment conditions. A novel type of time-survival curve was observed; the number of surviving cells decreased within a few minutes of treatment, then showed a transient increase after which there was again a decrease then an increase which reached a constant level in 3 hours. The increase in the surviving fraction of cells during the treatment period is interpreted as being due to recovery from the potentially lethal NCS damage manifested on the decrease of NCS activity in the medium. The subsequent fluctuation in the surviving fraction is not readily explainable, but may be due to reactivation and re-inactivation of NCS in the cells.