SURVIVAL AND CYCLE-PROGRESSION DELAY OF HUMAN LYMPHOMA-CELLS INVITRO EXPOSED TO VP-16-213

  • 1 January 1976
    • journal article
    • research article
    • Vol. 60  (9) , 1295-1306
Abstract
The lethal and kinetic effects of VP-16-213 [4''-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-.beta.-D-glucopyranoside] 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 h, 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 a 3 .mu.g/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; cells in S phase were most effectively blocked in the subsequent G2 phase. Continuous treatment with concentrations of VP-16-213 (> 0.5 .mu.g/ml for > 3 h) caused a retardation of S-phase transit with prompt recovery after drug release. Treatment with 10.0 .mu.g/ml for > 3 h 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.

This publication has 2 references indexed in Scilit: