CAMPTOTHECIN CAUSES CELL-CYCLE PERTURBATIONS WITHIN T-LYMPHOBLASTOID CELLS FOLLOWED BY DOSE-DEPENDENT INDUCTION OF APOPTOSIS

We have investigated the effect of the anticancer compound, camptothec in on Jurkat T-cells, a lymphoblastoid leukemic cell-line. Exposure to low concentrations led to rapid cessation of DNA (more than 95%) and RNA (more than 75%) synthesis. Perturbations to the cell cycle were ob served following exposure which caused a significant accumulation of c ells within G1 (P=0.03) with a concomitant decrease in G2/M (P=0.025), Concentrations below 0.1 mu M could inhibit DNA synthesis but not ind uce apoptosis. Induction of apoptosis was dose dependent and could be detected as early as 3 h post exposure, The apoptotic population appea red to be derived from G1 and S-phase cells but not G2/M, coinciding w ith the cell cycle compartments in which DNA and RNA polymerases funct ion. However, direct inhibition of DNA polymerase alone was not shown to be associated the induction of apoptosis or with a decrease in susc eptibility to camptothecin-induced cell death, The effects of camptoth ecin on Jurkat T-cells and the potential mechanisms involved are discu ssed in the context of observations made in other transformed cell lin es, (C) 1997 Elsevier Science Ltd.