Summary
Bleomycin (BLM) inhibits cell proliferation of noninfected chick embryo fibroblasts by blocking their DNA synthesis selectively.
Chick embryo fibroblasts have been transformed by Schmidt-Ruppin D strain of Rous Sarcoma Virus. Transformation has been determined by a focus assay. Foci formation is strongly reduced by BLM.
Virus replication is inhibited by BLM in growing and confluent monolayer cells. This result might be explained by the observation that this drug reduces proliferation of growing and of confluent monolayer cells very sensitively. During the first 24 hours after infection the BLM inhibitory effect is more pronounced than in the case of BLM-application during the period 24–48 hours after infection. This result is explained by published results, showing that cell division is required only for the initiation of transcription of virus RNA but not for its maintenance. BLM has only little effect on virus growth in transformed cells, because in these cells initiation of transcription of virus RNA has already taken place before the drug was added.
From the data obtained it is concluded, that BLM inhibits growth of Rous Sarcoma Virus by blocking cell proliferation.
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Abbreviations
- BLM:
-
Bleomycin
- RSV:
-
Rous Sarcoma Virus
- CEF:
-
chick embryo fibroblasts
- CEF-RSV:
-
chick embryo fibroblasts transformed by RSV
- FFU:
-
Focus forming unit
- GM:
-
Growth medium
References
Green, M., Gerard, G. F.: RNA-directed DNA polymerase-properties and functions in oneogenic RNA viruses and cells. In: Progress in Nucleic Acid Research and Molecular Biology (W. E. Cohn, ed.) 187–334, New York and London: Academic Press, 1974.
Haidle, C. W., Weiss, K. K., Kuo, T. M.: Release of free bases from deoxyribonucleic acid after reaction with bleomycin. Molec. Pharmacol.8, 531–537 (1972).
Humphries, E. H., Temin, H. M.: Requirement for cell division for initiation of transcription of Rous sarcoma virus DNA. J. Virol.14, 531–546 (1974).
Ichikawa, T., Nakano, I., Hirokawa, I.: On bleomycin treatment in the urological field. Proceedings of the 6th International Congress of Chemotherapy, Vol. II, pp. 304–316, University of Tokyo Press, 1970.
Miyaki, M., Kuroda, J., Ono, T.: Chemotherapy and action of bleomycin on DNA. Igaku no Ayumi (Progress in Medicine)85, 72–78 (1973).
Müller, W. E. G., Zahn, R. K., Beyer, R.: Is “I-DNA” derived from nuclear DNA. Nature227, 1211–1212 (1970).
Müller, W. E. G., Yamazaki, Z., Breter, H. J., Zahn, R. K.: Action of bleomycin on DNA and RNA. Eur. J. Biochem.31, 518–525 (1972).
Müller, W. E. G., Yamazaki, Z., Zahn, R. K.: Bleomycin, a selective inhibitor of DNA-dependent DNA polymerase from oncogenic RNA viruses. Biochem. Biophys. Res. Commun.46, 1667–1673 (1972).
Müller, W. E. G., Yamazaki, Z., Zöllner, J. E., Zahn, R. K.: Action of bleomycin on programmed synthesis. Influence on DNA and RNA nucleases. FEBS Letters31, 217–221 (1973).
Müller, W. E. G., Totuska, A., Nusser, I., Zahn, R. K., Umezawa, H.: Bleomycin: Inhibitor of DNA synthesis in isolated enzyme systems as well as in intact cell systems. Biochem. Pharmacol.,24, 911–915 (1975).
Müller, W. E. G., Totsuka, A., Zahn, R. K., Umezawa, H.: Methode zur Bestimmung der Bleomycin-inaktivierenden Enzymaktivität in Geweben. Z. Krebsf. u. Klin. Onkol.,83, 151–162 (1975).
Richardson, A. G., Pierson, D. L., Leach, F. R.: The effect of phenethyl alcohol on bacillus subtilis transformation. II. Biochim. Biophys. Acta174, 267–281 (1969).
Smith, R. E., Bernstein, E. H.: Production and purification of large amounts of Rous sarcoma virus. Appl. Microbiol.25, 346–353 (1973).
Suzuki, H., Nagai, K., Yamaki, H., Tanaka, N., Umezawa, H.: Mechanism of action of bleomycin. Studies with the growing culture of bacterial and tumor cells. J. Antibiot. (Tokyo) Ser. A21, 379–386 (1968).
Takeshita, M., Horwitz, S. B., Grollman, A. P.: Bleomycin, an inhibitor of vaccinia virus replication. Virology60, 455–465 (1964).
Takeuchi, M., Yamamoto, T.: Effects of bleomycin on mouse transplantable tumors. J. Antibiot. (Tokyo) Ser. A.21, 631–637 (1968).
Temin, H. M.: Studies on carcinogenesis by avian sarcoma viruses. V. Requirement for new DNA synthesis and for cell division. J. Cell. Physiol.69, 53–64 (1967).
Terasima, T., Umezawa, H.: Lethal effect of bleomycin on cultured mammalian cells. J. Antibiot. (Tokyo) Ser. A23, 300–304 (1970).
Terasima, T., Yasukawa, M., Umezawa, H.: Breaks and rejoining of DNA in cultured mammalian cells treated with bleomycin. Gann61, 513–516 (1970).
Umezawa, H., Maeda, K., Takeuchi, T., Okami, Y.: New antibiotics, bleomycin A and B. J. Antibiot. (Tokyo) Ser. A19, 200–209 (1966).
Umezawa, H., Takeuchi, T., Hori, S., Sawa, T., Ishizuka, M.: Studies on the mechanism of antitumor effect of bleomycin on squamous cell carcinoma. J. Antibiot. (Tokyo) Ser. A25, 409–420 (1972).
Umezawa, H.: Studies on bleomycin: Chemistry and the biological action. Biomédicine18, 459–475 (1973).
Umezawa, H.: Igaku no ayumi (Progress in medicine)84, 631 (1973).
Vogt, P. K.: Focus assay of Rous sarcoma virus. In: Fundamental Techniques in Virology (K. Habel andN. P. Salzman, eds.) 198–211. New York and London: Academic Press, 1969.
Yamazaki, Z., Müller, W. E. G., Zahn, R. K.: Action of bleomycin on programmed synthesis. Influence on enzymatic DNA, RNA and protein synthesis. Biochim. Biophys. Acta308, 412–421 (1973).
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Totsuka, A., Müller, W.E.G. & Zahn, R.K. Bleomycin: Action on growth of oncogenic RNA viruses and on cell transformation. Archives of Virology 48, 169–179 (1975). https://doi.org/10.1007/BF01318149
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DOI: https://doi.org/10.1007/BF01318149