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).
Ozawa
S
S
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
Inaba
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D008954:Models, Biological; D013696:Temperature; D013997:Time Factors; D009353:Zinostatin / Q000493:pharmacokinetics / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D009353:Zinostatin