Summary
Asynchronously dividing mouse fibroblasts (L-cells) treated with the antitumor antibiotic Bleomycin show various rather specific morphological alterations. Many of the cells exposed to bleomycin assume a more or less epitheloid cell shape and are larger than untreated cells; in addition to an increase in nuclear size these cells often contain multiple nuclei. In most of the cells nuclei show an almost complete loss of peripheral condensed chromatin. The nucleolar hypertrophy initially observed is followed by a shrinkage and segregation of the nucleolar components.
The cytoplasmic alterations include dilatation of the cisternae of the rough endoplasmic reticulum as well as an increase of free, non membrane attached ribosomes, often arranged in spiral- and rosette-shaped polysemes; they are not specific for bleomycin.
Zusammenfassung
Asynchron wachsende Mäusefibroblasten (L-Zellen) ändern unter der Einwirkung von Bleomycin ihre typische Zellform. In den vergrößerten, teilweise epitheloiden Zellen finden sich häufig multiple Zellkerne; die Nucleolen sind vergrößert. Eine langdauernde Bleomycin-Behandlung führt hingegen zu einer Verkleinerung der Nucleolen, die häufig mit einer Segregation der nucleolären Bausteine einhergeht. Die auffallendsten ultrastrukturellen Veränderungen bestehen in einem nahezu vollständigen Verlust besonders des kondensierten randständigen Kernchromatins, in einer starken Erweiterung der Cysternen des rauhen endoplasmatischen Reticulums sowie in einer Zunahme der freien, nicht membrangebunden Ribosomen.
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References
Barranco,S.C., Humphrey,R. M.: The effects of bleomycin on survival and cell progression in Chinese hamster cells in vitro. Cancer Res. 31, 1218–1223 (1971)
Bornstein,R.S., Hungerford,D.A., Haller,G., Engstrom,P.F., Yabro,J.W.: Cytogenetic effects of bleomycin therapy in man. Cancer Res. 31, 2004–2007 (1971)
Cohen,A.M., Philips,F. S., Sternberg,S. S.: Studies on the cytotoxicity of bleomycin in the small intestine of the mouse. Cancer Res. 32, 1293–1297 (1972)
David,H.: Zellschädigung und Dysfunktion. In: Alfert,M., Bauer,H., Harding,V., Sandritter,W., Sitte,P. (Eds.): Protoplasmatologia, Bd. X, 1. Berlin-Heidelberg-New York: Springer 1970
Goldblatt,P.I.: The endoplasmic reticulum. In: Lima-de-Faria,A. (Ed.): Handbook of molecular cytology, Vol. 15 pp. 1101–1129 Amsterdam-London: North-Holland Publ. Comp. 1969
Haidle,C.W.: Fragmentation of deoxyribonucleic acid by bleomycin. Molec. Pharmacol. 7, 645–652 (1971)
Harada,T., Nishikawa,Y., Suzuki,T., Ho,K., Baba,S.: Bleomycin treatment for cancer of the thyroid. Amer. J. Surg. 122, 53–57 (1971)
Ichikawa,T.: Bleomycin a new antitumor antibiotic as a specific agent against the squamous cell carcinoma. J. Jap. Med. Ass. 61, 487–497 (1969)
Kanamoto,Y.: Effect of various anticancer agents on DNA polymerase. Gann 62, 121–129 (1971)
Kimura,K., Sakai,Y., Chihiro,K., Kashikawa,H., Kitahara,T., Inaki,J., Sakano,T., Fujita,H., Jizuka,N., Mikuni,M.: Chemotherapy of malignant lymphoma with special reference to effects of bleomycin. Jap. J. Clin. expt. Med. 27, 1593–1601 (1969)
Kimura,I., Onoshi,T., Kunimasa,I., Takano,J.: Treatrhent of malignant lymphomas with bleomycin. Cancer 29, 58–60 (1972)
Krishan,A.: Bleomycin-induced fine structural alterations in cultured mouse fibroblasts and human lymphocytes of neoplastic origin. Cancer Res. 33, 777–785 (1973)
Kuo,M.T., Haidle,Ch.: Characterization of chain breakage in DNA induced by bleomycin. Biochim. biophys. Acta (Amst.) 335, 109–114 (1973)
Lapis,K., Berhard,W.: The effect of mitomycin C on the nucleolar fine structure of KB-cells in cell culture. Cancer Res. 25, 628–645 (1965)
Madreiter,H., Osieka,R., Kaden,P., Mittermayer,C.: Some effects of bleomycin on mouse fibroblasts. Unpublished Results (1971)
Mittermayer,C., Kaden,P., Sandritter,W.: Untersuchungen an teilungssynchronen L-Zellen. I. Optimale Wachstumsbedingungen und Charakterisierung des synchronen Zellsystems. Histochemie 12, 67–74 (1968)
Mittermayer,C., Osieka,R., Madreiter,H.: Bleomycin: Wirkung auf DNS und Zellkernstrukturen in Mäusefibroblasten. Arch. Dermal. Forsch. 249, 401–410 (1974)
Mollenhauer,H.H.: Plastic embedding mixtures for use in electron-microscopy. Stain Technol. 39, 111–114 (1964)
Müller,W.E.G., Yamazaki,Z.-I., Breter,H.-J., Zahn,R.K.: Action of bleomycin on DNA and RNA. Europ. J. Biochem. 3, 518–525 (1972)
Nagai,K., Suzuki,H., Tanaka,N., Umezawa,H.: Decrease of melting temperature and single strand scission of DNA by bleomycin in the presence of 2-mercaptoethanol. J. Antibiot. 22, 569–573 (1969a)
Nagai,K., Yamaki,H., Suzuki,H., Tanaka,N., Umezawa,H.: The combined effects of bleomycin and sulfhydryl compounds on the thermal denaturation of DNA. Biochim. biophys. Acta (Amst.) 179, 165–171 (1969b)
Nagatsu,M., Okagaki,T., Richart,R., Lambert,A.: Effects of bleomycin on nuclear DNA in transplantable VX-2 carcinoma of rabbit. Cancer Res. 31, 992–996 (1971)
Ogawa,K., Onoe,T.: Nuclear changes produced by bleomycin in the 3-methylcholanthrene-induced mouse epidermal carcinoma cells. Gann 60, 503–507 (1969)
Ohama,K., Kadotani,T.: Cytologie effects of bleomycin on cultured human leukocytes. Japan. J. Human. Genet. 14, 293–297 (1970)
Oka,S., Sato,K., Nakai,Y., Kurita,K., Hashimoto,K., Oshibe,M.: Treatment of lung cancer with bleomycin. Sci. Rep. Res. Inst. Tohoku Univ. (Med.) 16, 30–36 (1969)
Omoto,S., Takita,T., Maeda,K., Umezawa,H., Umezawa,S.: The chemistry of bleomycin. VIII. The structure of the sugar moiety of bleomycin A2. J. Antibiot. 25, 752–754 (1972)
Ono,T.: Effect of bleomycin on the chromosome of HeLa cell. J. Jap. obstet, gynecol. Soc. 23, 376–384 (1971)
Paika,K.D., Krishan,A.: Bleomycin-induced chromosomal aberrations in cultured mammalian cells. Cancer Res. 33, 961–965 (1973)
Reynolds,E.S.: The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J. Cell Biol. 17, 208–212 (1963)
Reynolds,R.C., Montgomery,P. O., Hughes,B.: Nucleolar “caps” produced by actinomycin-D. Cancer Res. 24, 1269–1277 (1964)
Riede,U.N., Kaiser,W., v.Matt,Ch., Rohr,H.P.: Beeinflussung der quantitativen Cytoarchitektur der Rattenleberzelle durch das Cytostaticum Bleomycin. Z. Krebsforsch. 80, 323–334 (1973)
Saito,M., Andoh,T.: Breakage of a DNA-protein complex induced by bleomycin and their repair in cultured mouse fibroblasts. Cancer Res. 33, 1696–1700 (1973)
Shastry,S., Slayton,R.E., Wolter,J., Perlia,C.P., Taylor,S.G.: Clinical study with bleomycin. Cancer 28,1142–1146(1971)
Shiba,S., Terakawi,A., Taguchi,T., Kawamata,J.: Selective inhibition of formation of deoxyribonucleic acid in Escherichia coli by mitomycin C. Nature (Lond.) 183, 1056–1059 (1959)
Shirikawa,I., Azegami,M, Ishii,S.-I., Umezawa,H.: Reaction of bleomycin with DNA: strand scission of DNA in the absence of sulfhydryl or peroxide compounds. J. Antibiot. 24, 761–766 (1971)
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. 21, 379–386 (1968)
Suzuki,H., Nagai,K., Akutsu,E., Yamaki,H., Tanaka,N., Umezawa,H.: On the mechanism of action of bleomycin. Strand scission of DNA caused by bleomycin and its binding toDNA in vitro. Biochim. biophys. Acta (Amst.) 174, 309–314 (1969a)
Suzuki,H., Nagai,K., Yamaki,H., Tanaka,N., Umezawa,H.: On the mechanism of action of bleomycin: scission of DNA strands in vitro and in vivo. J. Antibiot. 22, 446–148 (1969b)
Takeda,K., Sagawa,Y., Arakawa,T.: Therapeutic effect of bleomycin for skin tumors. Gann 61, 207–218 (1970)
Takeuchi,M., Yamamoto,T.: Effects of bleomycin on mouse transplantable tumors. J. Antibiot. 21, 631–637 (1968)
Takita,T., Muraoka,Y., Yoshioka,T., Fujii,A., Maeda,K., Umezawa,H.: The chemistry of bleomycin. IX. The structures of bleomycin and phleomycin. J. Antibiot. 25, 755–758 (1972)
Terasima,T., Yasukawa,M., Umezawa,H.: Breaks and rejoining of DNA in cultured mammalian cells treated with bleomycin. Gann 61, 513–516 (1971)
Tobey,R.A.: A simple, rapid technique for determination of the effects of chemotherapeutic agents on mammalian cell-cycle traverse. Cancer Res. 32, 309–316 (1972)
Umezawa,H.: Bleomycin and other antitumor antibiotics of high molecular weight. Antimicrobial Agents Chemotherapy 1965, 1079–1085.
Umezawa,H., Ishizuka,M., Maeda,K., Takeuchi,T.: Studies on bleomycin. Cancer 20, 891–895 (1967)
Watanabe,M., Takabe,Y., Katsumata,T., Terasima,T.: Effects of bleomycin on progression through the cell cycle of mouse L-cells. Cancer Res. 34, 878–881 (1974)
Watson,M. L.: Staining of tissue sections for electron microscopy with heavy metals. J. biophys. biochem. Cytol. 4, 475–478 (1958)
Yamaki,H., Suzuki,H., Nagai,K.,Tanaka,N., Umezawa,H.: Effects of bleomycin A2 on deoxyribonuclease, DNA-polymerase, and ligase reactions. J. Antibiot. 24, 178–184 (1971)
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. Acta (Amst.) 308, 412–421 (1973)
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Madreiter, H., Osieka, R., Kaden, P. et al. Effect of bleomycin on the fine structure of mouse fibroblasts. Z. Krebsforsch. 85, 63–72 (1976). https://doi.org/10.1007/BF00308130
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DOI: https://doi.org/10.1007/BF00308130