| Abstract: | Acronycine — an alkaloid with antineoplastic activity against a wide range of experimental tumors — at concentrations of 0.5-12 μg/ml rapidly inhibits RNA synthesis in L5178Y mouse lymphoma and IRC rat monocytic leukemia cultures. Culture growth is arrested only at acronycine concentrations which markedly inhibit RNA synthesis. DNA synthesis is inhibited at rather higher concentrations but this is not a prerequisite of the arrest of growth. It is suggested that the arrest of growth may be a consequence of the inhibition of RNA synthesis. In both cultures arrest of growth coincides with the appearance of many cells with two apparently normal nuclei. Cells are not arrested in mitosis. It is shown these binucleated cells very probably arise from an inhibition of cell cleavage. Studies with synchronized cultures show that at low drug concentrations, more than one cell cycle may elapse before growth is arrested and binucleated cells appear, indicating the effect on cytokinesis is not immediate. The results suggest that the arrest of growth may be a result of a slow depletion of a component essential for cell cleavage. The disturbance at division is a major factor in arresting growth at low drug concentrations. At higher acronycine concentrations, when RNA synthesis may be inhibited by 80–90%, the cytotoxic effects appear earlier and are less specifically directed at cytokinesis; DNA synthesis is then also rapidly and markedly inhibited. |
