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Abstract

Strains of Streptomyces verticillus native to the soil of the coal mining country of Fukuoka Prefecture, Japan can elaborate heterogeneous antibiotic substances (i.e., phleomycin and bleomycin) with a capacity to block DNA synthesis, inhibit proliferation of replicative RNA’s, and prevent higher cells from entering meiotic or mitotic division. These actions can occur separately, possibly because they depend on different specific compounds present in phleomycin and bleomycin. These actions were discovered at different times and in different laboratories during independent investigations. Reported separately, they created a confusing and conflicting literature on the action of phleomycin-bleomycin.

Keywords

Antineoplastic Agent Minor Groove Levulinic Acid Penile Cancer Receptor Unit 
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References

  1. Adams, R. L. P., Abrams, R., Lieberman, I.: Rise in deoxyribonucleic acid polymerase activity in the absence of deoxyribonucleic acid synthesis in cultured kidney cells. Nature (Lond.) 206, 512–513 (1965).CrossRefGoogle Scholar
  2. Adams, R. L. P., Abrams, R., Lieberman, I.: Deoxycytidylate synthesis and entry into the period of deoxyribonucleic acid replication in rabbit kidney cells. J. biol. Chem. 241, 903–905 (1966).PubMedGoogle Scholar
  3. Bittar, E. E.: Effect of aldosterone on Na efflux in single Maia fibers. Biochem. biophys. Res. Comm. 23, 868–873 (1966).PubMedCrossRefGoogle Scholar
  4. Bittar, E. E.: Insulin and the sodium pump of the Maia muscle fiber. Nature (Lond.) 214, 726–727 (1967).CrossRefGoogle Scholar
  5. Bittar, E. E., Dick, D. A. T., Ery, D. J.: Effects of aldosterone on Na efflux in single oocytes of Bufo bufo. J. Physiol. 184, 23P (1966).Google Scholar
  6. Bradner, W. T., Pindell, M. H.: Antitumor properties of phleomycin. Nature (Lond.) 196, 683–684 (1962).CrossRefGoogle Scholar
  7. Bradner, W. T., Pindell, M. H.: Strain of stimulated regression of Sarcoma 180. Cancer Res. 25, 859–864 (1965).PubMedGoogle Scholar
  8. Bradner, W. T., Pindell, M. H.: Myeloid leukemia C149P as a screen for cancer chemotherapeutic agents. Cancer Res. 26, 375–390 (1966).PubMedGoogle Scholar
  9. Cavalieri, L.F.: Nucleic acids and information transfer. J. cell. comp. Physiol. 62, 111–122 (1963).CrossRefGoogle Scholar
  10. Djordjevic, B., Kim, J. H.: Lethal effect of phleomycin in different stages of the division cycle of HeLa cells. Cancer Res. 27, 2255–2260 (1967).PubMedGoogle Scholar
  11. Dold, U., Schmidt, C. G.: Cytostatically active antibiotics. Internist 12, 136–142 (1971).PubMedGoogle Scholar
  12. Falaschi,A., Kornberg, A.: Phleomycin, an inhibitor of DNA polymerase. Fed. Proc. 23, 940–945 (1964).Google Scholar
  13. Fanestil, D.: The mechanism of action of aldosterone on sodium transport; effect of inhibitors of DNA synthesis. Life Sci. 7, 191–195 (1968).CrossRefGoogle Scholar
  14. Fukatsu, H., Yoshida, K.: Three cases of penile cancer—clinical use of a new antineoplastic antibiotic, bleomycin. Iryo. 23, 694–697 (1969) (in Japanese).PubMedGoogle Scholar
  15. Giese, A. C.: Macromolecular synthesis during regeneration in Blepharisma determined by specific inhibitors and incorporation of carbon-14 labeled tracers. Exp. cell. Res. 61, 91–102 (1970).PubMedCrossRefGoogle Scholar
  16. Gorman, T., Pietsch, P.: Strategy for crystallographic analysis of phleomycin-DNA complexes: Fournier transforms. Physiol. Chem. Phys. 1, 312–316 (1969).Google Scholar
  17. Grigg, G. W.: Induction of DNA breakdown and death in Escherichia coli by phleomycin. Its association with dark-repair processes. Molec. gen. Genetics 104, 1–11 (1969).Google Scholar
  18. Grigg, G. W.: Amplification of phleomycin induced death and DNA breakdown by caffeine in Escherichia coli. Molec. gen. Genetics 107, 162–172 (1970).CrossRefGoogle Scholar
  19. Hanson, C. V.: A study of rapid hydrogen exchange in nucleic acids. J. molec. Biol. 58, 847–863 (1971).PubMedCrossRefGoogle Scholar
  20. Hasegawa, Y., Irikura,T., Mizuno, D.: Screening test for the prevention of metastasis produced by Ehrlich carcinoma cells. Chem. pharm. Bull. 18, 810–814 (1970).Google Scholar
  21. Hecht, T., Summers, D. F.: Effect of phleomycin on polio virus RNA replication. Virology 40, 441–447 (1970).PubMedCrossRefGoogle Scholar
  22. Heinemann, B., Howard, A. J.: Antiphage properties of compounds possessing both antitumor and inducing activities. Antimicrob. Ag. Chemother. 1964, 126–130 (1965a).Google Scholar
  23. Heinemann, B., Howard, A. J.: Effect of compounds with both antitumor and bacteriophage- inducing activities on Escherichia coli nucleic acid synthesis. Antimicrob. Ag. Chemother. 1964, 488–492 (1965b).Google Scholar
  24. Higuchi, M., Goto, K., Fujimoto, M., Namiki, O., Kikuchi, G.: Effect of inhibitors of nucleic acid and protein synthesis on the induced synthesis of bacteriochlorophyll and (5-amin- levulinic acid synthesis by Rhodopseudomonas spheroides. Biochim. biophys. Acta (Amst.) 95, 94–110 (1965).Google Scholar
  25. Honda, Y., Ohmori, K., Yoshida, K., Arai, K.: Experimental treatment of papilloma with bleomycin. Oto-Rhino-Laryngol. (Tokyo) 12, 247–252 (1969) (in Japanese).Google Scholar
  26. Hori, M., Ito, E., Umezawa, H.: Inhibitory effects of antitumor substances on growth and glycolysis of Yoshida rat sarcoma cells. J. Antibiot. A16, 1–6 (1963).Google Scholar
  27. Horwitz, S. B., Chang, S. C., Grollman, A. P., Bořkovec, A. B.: Chemosterilant action of anthramycin: a proposed mechanism. Science 174, 159–161 (1971).PubMedCrossRefGoogle Scholar
  28. Hotta, Y., Stern, H.: Action of phleomycin on meiotic cells. Cancer Res. 29, 1699–1706 (1969).PubMedGoogle Scholar
  29. Ichikawa, T.: On an antineoplastic agent, bleomycin. Naika 22, 630–633 (1968) (in Japanese).PubMedGoogle Scholar
  30. Ichikawa, T., Nakano, I., Hirokawa, I.: Bleomycin treatment of the tumors of penis and scrotum. J. Urol. 102, 699–707 (1969).PubMedGoogle Scholar
  31. Ichikawa, T.: A new antineoplastic agent, bleomycin—its effect on squamous cell carcinoma. J. Jap. med. Assoc. 61, 487–497, (1969a) (in Japanese).Google Scholar
  32. Ichikawa, T.: New antineoplastic agent, bleomycin, with special reference to its notable effect on squamous cell carcinoma. Jap. J. clin. Med. 27, 1618–1626 (1969b).Google Scholar
  33. Ichikawa, T.: Discovery of the effect of bleomycin on squamous cell carcinoma and development of its research. J. Jap. med. Assoc. 62, 153–158 (1969c) (in Japanese).Google Scholar
  34. Ichikawa, T., Matsijda, A., Miyamoto, K., Tsubosaki, M., Kaihara, T., Sakamoto, K., Umezawa, H.: Biological studies on bleomycin A. J. Antibiot. 20, 149–155 (1967).PubMedGoogle Scholar
  35. Ichikawa, T., Umezawa, H.: Clinical study on a new antitumor antibiotic, bleomycin. Proc. 5th Int. Congr. Chemotherapy 507 (1967).Google Scholar
  36. Iijima, T., Ikeda, Y.: Mutability of the phleomycin-resistant mutants of Bacillus subtilis. I. Isolation of genetically unstable mutants. J. gen. appl. Microbiol. 16, 419–427 (1970).CrossRefGoogle Scholar
  37. Ikeda, K., Egami, F.: Effects of antibiotics and antimetabolites on the induced formation of pyocin R. Z. Allg. Mikrobiol. 6, 219–225 (1966).CrossRefGoogle Scholar
  38. Ikeda, Y., Iijema, T., Tajima, K.: Elimination of F-episome from a male strain of Escherichia coli by treatment with sarkomycin and a related antibiotic. J. gen. appl. Microbiol. 13, 247–254 (1967).CrossRefGoogle Scholar
  39. Ikekawa, T., Iwami, F., Hiranaka, H., Umezawa, H.: Separation of phleomycin components and their properties. J. Antibiot. A17, 194–199, 1964.PubMedGoogle Scholar
  40. Inuyama, Y., Machukawa, J.: Effect of 5-fluorouracil and bleomycin on malignant head and neck tumors. Otolaryngol. 41, 901–909 (1969) (in Japanese).Google Scholar
  41. Ishizuka, M., Takayama, H., Takeuchi, T., Umezawa, H.: Studies on antitumor activity, antimicrobial activity and toxicity of phleomycin. J. Antibiot. A19, 260–271 (1966).PubMedGoogle Scholar
  42. Ishizuka, M., Takayama, H., Takeuchi, T., Umezawa, H.: Activity and toxicity of bleomycin. J. Antibiot. A20, 15–24 (1967).PubMedGoogle Scholar
  43. Iwata, A., Consigli, R. H.: Effect of phleomycin on polyoma virus synthesis in mouse embryo cells. J. Virol. 7, 29–40 (1971).PubMedGoogle Scholar
  44. Jacobs, N. F., Neu, R.L., Gardner, L. T.: Phleomycin-induced mitotic inhibition and chromosomal abnormalities in cultured human leukocytes. Mutat. Res. 7, 251–253 (1969).PubMedCrossRefGoogle Scholar
  45. Jaffe, J.: Sensitivity of Trypanosoma equiperdum to the action of tumor-inhibitory antibiotics in vivo. Nature (Lond.) 218, 704–705 (1967).CrossRefGoogle Scholar
  46. Jagiello, G. M.: Action of phleomycin on the meiosis of the mouse ovum. Mutat. Res. 6, 289–295 (1968).PubMedCrossRefGoogle Scholar
  47. Kajiwara, K., Kim, U. H., Mueller, G. C.: Phleomycin, an inhibitor of replication of HeLa cells. Cancer Res. 26, 233–236 (1966).PubMedGoogle Scholar
  48. Kanno, T., Kudo, T., Nakazawa, T., Takeuchi, T., Umezawa, H.: Bleomycin as an anti-brain tumor antibiotic. II. The distribution of 3H bleomycin A2(—Cu) in the experimental brain tumor of the mouse. Clin. Neurol. (Tokyo) 10, 501–506 (1970) (in Japanese).Google Scholar
  49. Kato, S., Hara, I., Abe, H., Ikeda, T., Yamagami, K., Uchiya, M., Shimomura, G.: Treatment for cancer of the female genital organs with an antineoplastic agent, bleomycin. Sanfujinka no Jissai 19, 204–215 (1970) (in Japanese).PubMedGoogle Scholar
  50. Kihlman, B. A., Odmark, G., Hartley, B.: Studies on the effects of phleomycin on chromosome structure and nucleic acid synthesis in Vicia faba. Mutat. Res. 4, 783–790 (1967).PubMedCrossRefGoogle Scholar
  51. Kimura, K., Sakai, Y., Konda, T., Kashiwada, N., Kitahara, T., Inagaki, J., Sakano, K., Fujita, H., Iizuka, N., Mikuni, M.: Chemotherapy of malignant lymphoma, with special reference to the effect of bleomycin. Jap. J. clin. Med. 27, 1593–1601 (1968) (in Japanese).Google Scholar
  52. Koch, G.: Differential effect of phleomycin on the infectivity of poliovirus and poliovirus- induced ribonucleic acids. J. Virol. 8, 28–34 (1971).PubMedGoogle Scholar
  53. Koyama, G., Nakamura, H., Muraoka, Y., Takita,T., Maeda, K., Umezawa, H.: The chemistry of bleomycin. II. The molecular and crystal structure of a sulfur-containing chromophoric amino acid. Tetrahedron Let. 44, 4635–4638 (1968).Google Scholar
  54. Kunimoto, T., Hori, M., Umezawa, H.: Modes of action of phleomycin, bleomycin, and formycin on HeLaS3 cells in synchronized culture. J. Antibiot. A20, 277–281 (1967).PubMedGoogle Scholar
  55. Lein, J., Heinemann, B., Gourevitch, A.: Induction of lysogenic bacteria as a method of detecting potential antitumor agents. Nature (Lond.) 196, 783–784 (1962).CrossRefGoogle Scholar
  56. Maeda, K., Kosaka, H., Yagishita, K., Umezawa, H.: A new antibiotic, phleomycin. J. Antibiot. A9, 82–85 (1956).PubMedGoogle Scholar
  57. Mattingly, E.: Induction of chromosome and chromatid type aberrations by phleomycin. Mutat. Res. 4, 51–57 (1967).PubMedCrossRefGoogle Scholar
  58. Mitsuhashi, S., Takahashi, H.: Drug-resistance of enteric bacteria 19. Stability of the transmissible drug-resistance (R) factor in the host cell. Gunma J. med. Sci. 13, 129 - 134 (1964).Google Scholar
  59. Mitsuya, H., Kondo, A., Senda, H., Yamanchi, T.: (Clinical study with bleomycin on penile cancer: experience in 5 cases.) Nishinihon J. Urol. 31, 270–272 (1969) (in Japanese).Google Scholar
  60. Muraoka, Y., Takita, T., Maeda, K., Umezawa, H.: Chemistry of bleomycin. IV. Structure of amine component II of bleomycin A2. J. Antibiot. 23, 252–253 (1970).PubMedGoogle Scholar
  61. Nagai, K., Suzijki, H., Tanaka, N., Umezawa, H.: Decrease of melting temperature and single strand scission of DNA by bleomycin in the presence of 2-mercaptoethanal. J. Antibiot. A22, 569–573 (1969a).PubMedGoogle Scholar
  62. Nagai, K., Suzuki, H., Tanaka, N., Umezawa, H.: Decrease of melting temperature and single strand scission of DNA by bleomycin in the presence of hydrogen peroxide. J. Antibiot. A22, 624–628 (1969b).PubMedGoogle Scholar
  63. 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 (1968).Google Scholar
  64. Nagatsu, M., Okagaki, T., Richart, R. M., Lambert, A.: Effects of bleomycin on nuclear DNA in transplantable VX-2 carcinoma of rabbit. Cancer Res. 31, 992–996 (1971).PubMedGoogle Scholar
  65. Nakamura, S., Murakami, Y., Hashiguchi, T., Kuga, G., Yanagi, Y., Fujimoto, N., Masuda, Y.: (Clinical and pathological observations on malignant tumors of the head and neck region treated with bleomycin.) Otolaryngol. 41, 465–477 (1969) (in Japanese).Google Scholar
  66. Nanjo, S., Suga, A.: (Case report of lingual papilloma—electron microscopic observation of bleomycin.) J. Otolaryngol. Jap. 73, 237–244 (1970) (in Japanese).Google Scholar
  67. Neubert, D.: Vergleichende Untersuchungen über die Nucleinsäuresynthese in Zellkernen und Mitochondrien und ihre Beeinflußbarkeit durch Pharmaka. Arch. exp. Pathol. Pharmakol. 253, 152–176 (1966).Google Scholar
  68. Oka, S., Sato, K., Nakai, Y., Kurita, K., Hashimoto, K., Oshibe, M.: Treatment of lung cancer with bleomycin. Sci. Rep. Res. Inst. Tahoku Univ. 16, 30–36 (1969).Google Scholar
  69. Palmer, W. M., Fridhandler, L.: Effects of growth-inhibiting antibiotics on macromolecule biosynthesis in preimplantation rabbit conceptus. Fertil. Steril. 19, 273–285 (1968).PubMedGoogle Scholar
  70. Pasternak, J., Samoiloff, M. R.: The effect of growth inhibitors on post-embryonic development in the free-living nematode, Pangrellus silusiae. Comp. Biochem. Physiol. 33, 27–38 (1970).PubMedCrossRefGoogle Scholar
  71. Pietsch, P.: Differences in DNA synthesis as reflected in variations in the acute inhibition of replication by the antibiotic, phleomycin. Anat. Ree. 157, 301 (1967a).Google Scholar
  72. Pietsch, P.: A structural hypothesis concerning the general mode of action of phleomycin, a specific inhibitor of DNA synthesis. Anat. Ree. 157, 402 (1967b).Google Scholar
  73. Pietsch, P.: Phleomycin: biological and chemical variations in different batches. Microbios. 1, 387–392 (1969a).Google Scholar
  74. Pietsch, P.: Structural events in DNA in transcription and replication: the influence of histones on in vitro reactions of actinomycin-D and phleomycin-909. Cytobios. 4, 375–391 (1969b).Google Scholar
  75. Pietsch, P., Clapper, G.: Receptivity of DNA to phleomycin. Cytobios. 1, 145–152 (1969).Google Scholar
  76. Pietsch, P., Corbett, C.: Competitive effects of phleomycin and mercuric chloride in vivo. Nature (Lond.) 219, 933–934 (1968).CrossRefGoogle Scholar
  77. Pietsch, P., Corbett, C., Briden, D.W., Jewett, G.: Diffusability of phleomycin studied by means of neutron activation analysis. Physiol, ehem. Phys. 1, 232–236 (1969).Google Scholar
  78. Pietsch, P., Eng, R.: Phleomycin: enhancement of properties by treatment with acid. Microbios. 1, 213–231 (1969).Google Scholar
  79. Pietsch, P., Garrett, H.: Primary site of reaction in the in vitro complex of phleomycin in DNA. Nature (Lond.) 219, 488–489 (1968).CrossRefGoogle Scholar
  80. Pietsch, P., Garrett, H.: Phleomycin: evidence of in vivo binding to DNA. Cytobios. 1, 7–15 (1969a).Google Scholar
  81. Pietsch, P., Garrett, H.: Phleomycin induced changes in the ultrastructure of DNA. Biophys. J. A9, 126 (1969b).Google Scholar
  82. Pietsch, P., McCollister, S. B.: Replication and the activation of muscle differentiation. Nature (Lond.) 208, 11702–1173 (1965).CrossRefGoogle Scholar
  83. Pitts, J., Sinsheimer, R. L.: Effect of phleomycin on replication of bacteriophage 0X174. J. molec. Biol. 15, 676–680 (1966).PubMedCrossRefGoogle Scholar
  84. Price, K. E., Bradner, W. T., Buck, R. E., Lein, J.: Synergistic antimicrobial and antitumor effects of phleomycin and fluorinated pyrimidines. Antimicrob. Ag. Chemother. 1904, 481–487 (1965).Google Scholar
  85. Price, K. E., Buck, R. E., Lein, J.: System for detecting inducers of lysogenic Escherichia coli W1709 (A) and its applicability as a screen for antineoplastic antibiotics. Appl. Microbiol. 12, 428–435 (1964).PubMedGoogle Scholar
  86. Price, K. E., Buck, R. E., Lein, J.: Incidence of antineoplastic activity among antibiotics found to be inducers of lysogenic bacteria. Antimicrob. Ag. Chemother. 1964, 505–517 (1965).Google Scholar
  87. Printz, M. P., von Hippel, P. H.: Hydrogen exchange studies of DNA structure. Proc. nat. Acad. Sci. (Wash.) 58, 363–370 (1965).CrossRefGoogle Scholar
  88. Rakieten, N., Nadkarni, M.V., Rakieten, M. L., Gordon, B.S.: Toxicologic and pharmacologic evaluation of phleomycin, including special studies on its nephrotoxicity. Toxicol, appl. Pharmacol. 14, 590–602 (1969).Google Scholar
  89. Redon, H.: Study of the clinical efficiency of bleomycin in human cancer. Brit. med. J. 2, 643–645 (1970).CrossRefGoogle Scholar
  90. Richmond, J. E., Glaeser, R. M., Todd, P.: Protein synthesis and aggregation of embryonic cells. Exp. Cell Res. 52, 43–58 (1968).PubMedCrossRefGoogle Scholar
  91. Smale, B. C., Montgillion, M. D., Pridham, T. G.: Phleomycin, an antibiotic markedly effective for control of bean rust. Plant Dis. Rep. 45, 244 (1961).Google Scholar
  92. Sober, H. A.: Handbook of Biochemistry. Selected data for molecular biology. Cleveland: The Chemical Rubber Co. 1968.Google Scholar
  93. Suzuki, H.: On the mechanism of action of bleomycin: scission of DNA strands in vitro and in vivo. J. Antibiot. 22, 446–448 (1969b).PubMedGoogle Scholar
  94. Suzuki, H., Nagai, K., Akutsu, E., Yamaki, H., Tanaka, N., Umezawa, H.: Mechanism of action of bleomycin. Strand scission of DNA caused by bleomycin and its binding to DNA in vitro. J. Antibiot. 28, 473–480 (1970).Google Scholar
  95. 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. A21, 379–386 (1968).PubMedGoogle Scholar
  96. 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, 446–468 (1969a).PubMedGoogle Scholar
  97. Suzuki, M., Murai, A., Watanabe, A., Nunokawa, O.: Treatment of cancer of the female genital organs with a new anti-cancer agent, bleomycin. Acta med. biol. 17, 259–275 (1970).PubMedGoogle Scholar
  98. Suzuki, M., Nomura, H., Ito, M., Kasamatu, T., Nakanishi, K., Yamaoka, S., Misoo, Y., Takamisawa, Y., Suzuki, T., Takeda, T., Iizima, H., Kuto, J., Kinoshita, S., Moriya, K., Murai, J., Hasegawa, K., Watanabe, K., Ootake, S., Fushekawa, O.: Therapy of cancer of the female genitalia with a new antineoplastic drug, bleomycin—basic study of bleomycin. Sanfujin Jissai 18, 375–379 (1969a) (in Japanese).Google Scholar
  99. Suzuki, M., Nomura, H., Ito, M., Kasamatu, T., Nakanishi K., Yamaoka, S., Misoo, Y., Takamisawa, Y., Suzuki, T., Takeda, T., Iizima, H., Kuto, J., Kinoshita, S., Moriya, K., Murai, J., Hasegawa, K., Watanabe, K., Ootake, S., Fushekawa, O.: Therapy of gynecologic tumors with a new antineoplastic agent, bleomycin—clinical study. Sanfujin Jissai 18, 574–581 (1969b) (in Japanese).Google Scholar
  100. Suzuki, Y., Miyake, K.: Clinical use of bleomycin in malignant tumor of the head and neck. J. Jap. med. Assoc. 62, 112–117 (1969) (in Japanese).Google Scholar
  101. Takeda, K., Sawawa, Y., Arakawa, T.: Therapeutic effects of bleomycin for skin tumors. Gann 61, 207–218 (1970) (in Japanese).PubMedGoogle Scholar
  102. Takeuchi, M., Yamamoto, T.: Effects of bleomycin on mouse transplantable tumors. J. Antibiot. A21, 631–637 (1968).PubMedGoogle Scholar
  103. Takeuchi, T.: Inhibition of resistant dysentery bacilli by phleomycin. J. Antibiot. A16, 172 (1963).PubMedGoogle Scholar
  104. Takita, T.: Studies on purification and properties of phleomycin. J. Antibiot. A12, 285–289 (1959).PubMedGoogle Scholar
  105. Takita, T., Maeda, K., Umezawa, H.: Chemistry of bleomycin. III. The sugar moieties of bleomycin A2. J. Antibiot. A22, 237–239 (1969).PubMedGoogle Scholar
  106. Takita, T., Muraoka, Y., Maeda, K., Umezawa, H.: Chemical studies on bleomycin. I. The acid hydrolysis products of bleomycin A2. J. Antibiot. A21, 79–80 (1968).PubMedGoogle Scholar
  107. Tanaka, N.: Effect of phleomycin on DNA polymerase of tumor origin. J. Antibiot. A18, 111 (1965).PubMedGoogle Scholar
  108. Tanaka, N.: Inhibition of transcription by pluramycin and bleomycin. J. Antibiot. A28, 523–530 (1970).Google Scholar
  109. Tanaka, N., Yamaguchi, H., Umezawa, H.: Mechanism of action of phleomycin. J. Antibiot. A16, 86–91 (1963a).Google Scholar
  110. Tanaka, N., Yamaguchi, H., Umezawa, H.: Mechanism of action of angustmycins, mikamycins, and phleomycin. Jap. J. med. Sci. Biol. 16, 240–246 (1963b).PubMedGoogle Scholar
  111. Tanaka, N., Yamaguchi, H., Umezawa, H.: Mechanism of action of phleomycin, a tumorinhibitory antibiotic. Biochem. biophys. Res. Commun. 10, 171–174 (1963c).Google Scholar
  112. Tepper, H.B., Hollis, C.A., Galson, E.C., Sondheimer, E.: Germination of Fraxinus ornus embryos with and without phleomycin. Plant Physiol. 42, 1483–1486 (1967).CrossRefGoogle Scholar
  113. Terasima, T., Umezawa, H.: Lethal effect of bleomycin on cultured mammalian cells. J. Antibiot. A23, 300–304 (1970).PubMedGoogle Scholar
  114. Tevethia, F., Rapp, F.: Effect of phleomycin on the replication of papova virus SV40 and other DNA viruses in simian cells. Cancer Res. 29, 912–917 (1969).PubMedGoogle Scholar
  115. Tomizawa, H., Takahashi, H.: Stimulation of pectolytic enzyme formation of Erwinia aroides by nalidixic acid, mitomycin C and bleomycin. Agr. Biol. Chem. 35, 191–200 (1971).CrossRefGoogle Scholar
  116. Tsuboi, A., Terasima, T.: Rejoining of single breaks of DNA induced by x-rays in mammalian cells: effects of metabolic inhibitors. Molec. gen. Genetics 108, 117–128 (1970).CrossRefGoogle Scholar
  117. Ueno, M.: Clinical use of bleomycin in cases of cancer of the oral cavity. J. Jap. med. Assoc. 62, 117–126 (1969) (in Japanese).Google Scholar
  118. Umezawa, H.: Bleomycin and other antitumor antibiotics of high molecular weight. Antimicrob. Ag. Chemother. 1965, 1079–1085 (1966).Google Scholar
  119. Umezawa, H.: Index of antibiotics from actinomycetes. Tokyo: University Park Press and University of Tokyo Press 1967.Google Scholar
  120. Umezawa, H., Hori, M., Ishizuka, M., Takeuchi, T.: Studies on antitumor effect of phleomycin. J. Antibiot. A15, 274–275 (1962).Google Scholar
  121. Umezawa, H., Ishizuka, M., Hori, S., Chimura, H., Takeuchi, T., Komai, T.: The distribution of 3H-bleomycin in mouse tissue. J. Antibiot. A21, 638–642 (1968b).PubMedGoogle Scholar
  122. Umezawa, H., Ishizuka, M., Kimura, K., Iwanaga, J., Takeuchi,T.: Biological studies on individual bleomycins. J. Antibiot. A21, 592–602 (1968a).PubMedGoogle Scholar
  123. Umezawa, H., Ishizuka, M., Maeda, K., Takeuchi, T.: Studies on bleomycin. Cancer 20, 891895 (1967).Google Scholar
  124. Umezawa, H., Maeda, K.: Phleomycin, a new antibiotic substance. Japanese patent publication 2598/59, filed December 22, 1955 (translated by Kawase and Okada, Tokyo, 1959 ).Google Scholar
  125. Umezawa, H., Maeda, K., Takeuchi, T., Okami, Y.: New antibiotics, bleomycin A and B. J. Antibiot. A19, 200–209 (1966a).PubMedGoogle Scholar
  126. Umezawa, H., Suhara, Y., Ikekawa, T., Ishizuka, M., Hori, M., Maeda, K., Tanaka, N., Takeuchi, T.: Antitumor substances selected from streptomyces products. Int. Congr. Chemother. 1963, 974–978 (1964).Google Scholar
  127. Umezawa, H., Suhara, Y., Takita, T., Maeda, K.: Purification of bleomycins. J. Antibiot. A19, 210–215 (1966b).PubMedGoogle Scholar
  128. Watanabe, M., August, J. T.: Replication of RNA bacteriophage R23. II. Inhibition of phage specific UNA synthesis by phleomycin. J. molec. Biol. 33, 21–33 (1968).PubMedCrossRefGoogle Scholar
  129. Welsh, R., Vyska, K.: Properties of a new form of DNA from whole calf thymus nuclei: evidence for reactive special sites in DNA. Arch. Biochem. Biophys. 142, 132–143 (1971).PubMedCrossRefGoogle Scholar
  130. Werner, R.: Nature of DNA precursors. Nature New Biol. 233, 99–103 (1971).PubMedGoogle Scholar
  131. Yamagata, S., Uzuka, Y., Kurokawa, Y., YoSahara, M.: Cancer chemotherapy. Current status and prospects. J. Jap. Soc. Cancer Ther. 3, 8–17 (1968) (in Japanese).Google Scholar
  132. Yamaki, H., Tanaka, N., Umezawa, H.: Effects of several tumor-inhibitory antibiotics on immunological responses. J. Antibiot. A22, 315–321 (1969).PubMedGoogle Scholar
  133. Zimmer, D. E.: Efficacy of some antifungal substances for scontrol of seedling safflower rust. Plant Dis. Rep. 49, 623–626 (1965).Google Scholar

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© springer-Verlag Berlin-Heidelberg 1975

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  • Paul Pietsch

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