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Studies on the Mechanism of Inhibition by Polyenic Antibiotics of Nucleic Acid Biosynthesis in Ascites Tumor Cells

Istituto di Chimica Biologica, University of Rome and Centro di Biologica Molecolare del C. N. R., Rome 00185, Italy

The polyenic antibiotic lucensomycin caused a severe inhibition of uridine or thymidine incorporation into RNA or DNA of ascites tumor cells. The inhibition appeared to be related to the ability of the polyene to interact with the cell membrane, the permeability of which was increased; simple leakage of precursors or of enzymes from the cells did not fully account for the kinetics of inhibition.

Lucensomycin did not affect DNA or RNA synthesis, starting from triphosphonucleotides, by isolated nuclei. In the presence of the polyene, the cells became permeable to externally added nucleotides, which they could utilize for RNA or DNA synthesis. Nucleosides, even at high concentrations, could not substitute for nucleotides.

Received 7/12/71. Accepted 12/ 1/71.