Bleomycin: Chemical, Biochemical, and Biological Aspects : Proceedings of a Joint U.S.-Japan Symposium Held at the East-West Center, Honolulu, July 18–22, 1978

This book records the proceedings of a joint U.S.-Japan symposium on the chem­ istry, biochemistry, and biology of bleomycin, an antitumor antibiotic shown to be effective therapeutically against, eg, squamous cell carcinomas, Hodgkin's lymphoma, and testicular tumors. Several important and previously unreported observations were presented and the status of experimental work in the United States and Japan was reviewed; a summary and interpretation of the scientific presentations at the meeting has been prepared by the editor and is included as the first contribution in this volume. In addition to the symposium contributions, an experimental section has been included at the end of the book dealing with practical methods for the fractiona­ tion, modification, and assay of bleomycin. It is hoped that this section will facilitate progress in this area of scientific endeavor. The symposium from which this book is derived was organized by Drs. Umezawa, Takita, and Hecht and supported financially by the National Science Foundation, the National Cancer Institute, and the Japan Society for the Promotion of Science. S. M. Hecht v Contents Status Reports Summary of the Bleomycin Symposium. S. M. HECHT .............. 1 Advances in Bleomycin Studies. H. UMEZAWA ................... , 24 Review of the Structural Studies on Bleomycin. T. TAKITA . . . . . . . .. . . 37 . Synthetic and Biosynthetic Studies Studies on the Total Synthesis of Bleomycin. S. M. HECHT, D. 1. BURLETT, Y. MUSHIKA, Y. KURODA, and M. D. LEVIN .......... 48 A Synthetic Approach to the Pyrimidine Moiety of Bleomycin. Front Matter....Pages N1-xi Summary of the Bleomycin Symposium....Pages 1-23 Advances in Bleomycin Studies....Pages 24-36 Review of the Structural Studies on Bleomycin....Pages 37-47 Studies on the Total Synthesis of Bleomycin....Pages 48-62 A Synthetic Approach to the Pyrimidine Moiety of Bleomycin....Pages 63-74 Biogenetic Aspects of Bleomycin-Phleomycin Group Antibiotics....Pages 75-91 Liquid Chromatography of Bleomycin....Pages 92-105 NMR Study of Bleomycin....Pages 106-123 1 H-NMR Study of the Metal-Binding Sites of Bleomycin....Pages 124-136 The Metallobleomycins....Pages 137-155 Metal Complex of Bleomycin and Its Implication for the Mechanism of Bleomycin Action....Pages 156-164 Electron Spin Resonance Studies of 1:1:1 Bleomycin-Cobalt(II)-Qxygen Adduct Complex....Pages 165-169 A Role for Iron in the Degradation of DNA by Bleomycin....Pages 170-183 Contribution of the Superoxide Anion-Hydroxyl Radical Pathway to the Cleavage of DNA by Bleomycin....Pages 184-194 Interaction of Bleomycin with DNA....Pages 195-206 A Molecular Basis for the Interaction of Bleomycin with DNA....Pages 207-221 Molecular Aspects of Bleomycin-Promoted Damage of Covalently Closed Circular DNA....Pages 222-243 The Use of Covalently Closed Circular DNA to Investigate Properties of Bleomycin and Its Analogs....Pages 244-254 The Action of Bleomycin on DNA....Pages 255-266 Polyamines and the Toxicity of the Bleomycins....Pages 267-286 Cytotoxicity of Various Bleomycins to Cultured Mammalian Cells....Pages 287-296 Upward-Concave Dose-Response Relationship in Bleomycin Lethality of Mammalian Cells....Pages 297-308 Conjugation of Bifunctional Chelating Agents to Bleomycin for Use in Nuclear Medicine....Pages 309-323 Bleomycin-Induced Pulmonary Toxicity: A Model for the Study of Pulmonary Fibrosis....Pages 324-335 Concluding Remarks at the Symposium on Bleomycin....Pages 336-340 A Practical Method for the Separation of Bleomycin Components....Pages 341-342 Preparation of Bleomycinic Acid from Bleomycin A 2 ....Pages 343-344 A Practical Method for Preparing Copper-Free Bleomycin A 2 ....Pages 345-345 A Simple Assay for Bleomycin Activity: Degradation of Radioactive DNA to Acid-Soluble Products (1,2) ....Pages 346-347 Erratum to: Summary of the Bleomycin Symposium....Pages 352-352 Erratum to: The Metallobleomycins....Pages 353-353 Erratum to: A Molecular Basis for the Interaction of Bleomycin with DNA....Pages 354-354 Back Matter....Pages 349-351