Kinetic response of cultured human lymphoid cells to rubidazone

Analysis of rubidazone, the benzoylhydrazone derivative of daunorubicin, for its effects on cell cycle progression of a human lymphoid cell line showed a kinetic response pattern similar to that of adriamycin. Thus rubidazone induced a G₂-block, the magnitude and duration of which were dependent on concentration and incubation time. However, in contrast to adriamycin, a marked phase-dependent sensitivity for the induction of G₂-accumulation was observed; cells treated in early and mid-S-phase were most sensitive. This age-dependent kinetic response may account for the smaller G₂-accumulation in asynchronous cultures and the closer correlation of the magnitude of this kinetic effect with concentration and duration of rubidazone treatment. Prolonged exposure to high concentrations of rubidazone also delayed the traverse through G₁ and/or the G₁-S transition, whereas the S-phase transit was not impaired. Interference with cell cycle progression through G₁ into S-phase caused a stepwise accumulation of cells in G₂-phase.