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Mechanism of Action of Daunomycin*

Published online by Cambridge University Press:  01 August 2014

A. Di Marco
A. Di Marco*
Affiliation:
Istituto Nazionale Tumori, Milano

Summary

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Daunomycin (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.

Type
Research Article
Information
Acta geneticae medicae et gemellologiae: twin research , Volume 17 , Issue 1 , January 1968 , pp. 102 - 121
Copyright
Copyright © The International Society for Twin Studies 1968

Footnotes

*

These researches have been supported by the National Research Council (C.N.R.) - Committee for Biology and Medicine.

References

Arcamone, F. et al. (1964 a). Daunomycin, the structure of Daunomycinone. J. Amer. Chetn. Soc., 86: 5334.Google Scholar
Arcamone, F. et al. (1964 b). Daunomycin. II — The structure and stereochemistry of Daunosamine. J. Amer. Chetn. Soc., 86: 5335.Google Scholar
Bollum, F. J. (1963). Primers in DNA-polymerase reaction. In: Davidson and Cohn, Progress in Nucleic Acids Research. Academic Press.Google Scholar
Brockmann, H. (1963). Die Actinomycine. Fortschr. Org. Naturstoffe, 21: 121.Google Scholar
Calendi, E. et al. (1965). On physico-chemical interactions between Daunomycin and nucleic acids. Biochem. Biophys. Acta, 103: 25.Google Scholar
Costa, G., Astaldi, G. (1964). Effetto della Daunomicina sull'attività prolilerativa di cellule staminali ottenute in cultura da sangue umano normale. Tumori, 50: 477.Google Scholar
Davidson, J. N., Smellie, R. M. S. (1952). Phosphorous compound in the cell. Biochem. J., 52: 599.Google Scholar
Di Marco, A., Dasdia, T. (1966). Personal Communication.Google Scholar
Di Marco, A., et al. (1964). Daunomycin, a new antibiotic of the Rhodomycin group. Nature, 201: 706.CrossRefGoogle Scholar
Di Marco, A., Dasdia, T. et al. (1966). Unpublished data.Google Scholar
Di Marco, A., et al. (1965). Nucleolar and chromosomal origin of nuclear RNA and its passage to cytoplasm. Riv Ital. Istochim., 11: 211.Google Scholar
Di Marco, A., et al. (1965 b). Inhibiting effect of the new cytotoxic antibiotic Daunomycin on nucleic acid synthesis and mitotic activity of Hela cells. J. Cell. Biol., 27: 545.Google Scholar
Di Marco, A., et al. (1963). Ricerche sull'attività della Daunomicina su cellule normali e neoplastiche coltivate in vitro. Tumori, 49: 236.Google Scholar
Georgiev, G. P. et al. (1963). Biosynthesis of messenger and ribosomal ribonucleic acids in the nucleolochromosomal apparatus of animal cells. Nature. 200: 1292.Google Scholar
Grein, A. et al. (1963). Descrizione e classificazione di un attinomicete (Streptomyces peucetius sp. nova) produttore di una sostanza ad attività antitumorale: la Daunomicina. G. Microbiol., 11: 109.Google Scholar
Hartmann, G. et al. (1964). Hemmung der DNA-abhangigen RNA und DNA-synthese durch Antibiotica. Biochem. Z. 341: 126.Google Scholar
Lermann, H. H. (1962). A rapidly labeled RNA in rat liver nuclei. J. Molec. Biol., 5: 217.Google Scholar
Lermann, L. S. (1964). Acridine mutagen and DNA structure. J. Cell. Comp. Physiol., 64: 1 (Suppl.).CrossRefGoogle Scholar
Perry, R. (1963). Selective effects of Actinomycin D in the intracellular distribution of RNA synthesis in tissue culture cells. Exp. Cell. Res., 29: 400.CrossRefGoogle Scholar
Rusconi, A., Calendi, E. (1964). Azione della Daunomicina sulla sintesi nucleica in cellule di epatoma. Tumori, 50: 261.Google Scholar
Rusconi, A., Calendi, E. (1966). Action of Daunomycin on nucleic acid metabolism in Hela cells. Bioch. Biophys. Acta, 119: 413.Google Scholar
Silvestrini, R. et al. (1963). Azione della Daunomicina sul metabolismo degli acidi nucleici di cellule normali e neoplastiche coltivate in vitro. Tumori, 49: 399.CrossRefGoogle ScholarPubMed
Ward, C. et al. (1965). Base specificity in the interaction of polynucleotides with antibiotic drugs. Science, 149: 1259.Google Scholar