Mechanism of Action of Daunomycin

Abstract

SummaryDaunomycin (Da) a metabolite of Streptomyces peucetius has a cytotoxic and antimitotic activity on normal and neoplastic mammalian cells grown in vitro and strongly inhibits a variety of experimental tumors.The cell damage induced by Da is mainly nuclear.A finely granular appearance of the chromatin and marked alterations in shape and size of nucleoli in resting cells and many mitotic aberrations in mitotic cells were observed.Biochemical and autoradiographic researches show that the binding of Da with DNA causes a reduction of the DNA and RNA synthesis, especially of the RNA which is synthesized in the nucleoli and then passes into the cytoplasmic ribosomic RNA.Treatment with Da on synchronized cells shows a marked drop of the mitotic index and appearance of mitotic anomalies when the cells are treated in S and G2 phases.This reduction keeps also in the second mitotic wave. A reduction of the mitotic activity is observed also if the cells are treated near the middle of the interphase.Da causes a reduction in the percentage of the nuclei labelled with 3H thymidine and in the number of grains per nucleus, when the cells are treated in S phase, in the very beginning and middle of interphase.