Kinetic analysis of the in vitro cell-killing action of neocarzinostatin.

The relationship between the drug concentration and exposure time of neocarzinostatin (NCS) for a definite cell-killing effect was kinetically analyzed, taking into consideration its loss in biological activity during incubation. Its cell-killing activity was determined by a colony-forming inhibition assay, which was conducted at room temperature (25 degrees C) for 0.5-30 min exposure and at 37 degrees C for 5 min - 96 h exposure. Drug degradation at both temperatures was also investigated by bioassay. NCS lost its biological activity much faster at 37 degrees C than at 25 degrees C and the rate of loss in activity was higher at the lower initial concentration. Thus, the initial NCS concentrations necessary for 90% cell kill corresponding to each exposure time and a drug degradation constant were applied to a mathematical equation for the cell-killing effect of cell-cycle-phase-nonspecific agents. As a result, the curves for IC90-exposure time relationships predicted from drug degradation constants for 37 degrees C and 25 degrees C were fairly well fitted to the respective experimental data. These results indicate that the cell-killing action of NCS can be expressed by this mathematical equation with scrutiny of drug degradation and is dependent on the concentration-time product (C x T).