Survival and cycle-progression delay of human lymphoma cells in vitro exposed to VP-16-213.
The lethal and kinetic effects of VP-16-213 were analyzed in a human lymphoid cell line (T1 cells) in vitro. When asynchronous T1 cells were exposed to increasing concentrations of VP-16-213 for 1 hour, an exponential survival curve with a Do (mean lethal dose equal to the concentration required to reduce survival by 63% on the exponential part of the survival curve) of 3 mug/ml was obtained. Increasing exposure time also reduced survival exponentially. Synchronized cells showed age-dependent sensitivity to VP-16-213 with the greatest lethal damage experienced by cells treated in S and G2 phase. The major kinetic response of the T1 cells to VP-16-213 was a delay in G2 phase, the extent and duration of which was a function of drug concentration, exposure time, and cell cycle stage of drug addition; thus, cells in S phase were most effectively blocked in the subsequent G2 phase. Continuous treatment with concentrations of VP-16-213 (greater than 0.5 mug/ml for greater than 3 hours) caused a retardation of S-phase transit with prompt recovery after drug release. Treatment with 10.0 mug/ml for greater than 3 hours resulted in a "frozen state" of the whole life cycle, inducing only minor compartment changes. DNA synthesis was inhibited in the majority of cells with an S-phase DNA content. There was no correlation between the extent of perturbation and lethal effects after treatment with VP-16-213.
D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D008223:Lymphoma / Q000473:pathology; D009374:Neoplasms, Experimental / Q000473:pathology; D011034:Podophyllotoxin / Q000031:analogs & derivatives*
D005047:Etoposide; D011034:Podophyllotoxin