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Effects of acronycine on nucleic acid synthesis and population growth in mammalian tumor cell cultures
Author(s) -
Gout P. W.,
Dunn B. P.,
Beer C. T.
Publication year - 1971
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1040780116
Subject(s) - cytokinesis , dna synthesis , biology , mitosis , rna , binucleated cells , cell growth , cleavage (geology) , cell division , nucleic acid , microbiology and biotechnology , cell , cell culture , population , interphase , dna , biochemistry , chemistry , genetics , toxicity , micronucleus , paleontology , demography , organic chemistry , fracture (geology) , sociology , gene , micronucleus test
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.