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DNA Strand Scission by Activated Bleomycin Group Antibiotics

  • Sidney M. Hecht

Abstract

The bleomycins (BLMs) are a family of antitumor antibiotics used clinically for the treatment of squamous cell carcinomas and malignant lymphomas (1–4). Bleomycin A2 is the major constituent of the clinically used mixture of bleomycins. Although biochemical studies have indicated several loci that may contribute to the overall therapeutic effects obtained with bleomycin, the accumulated evidence suggests that the primary effect is at the level of oxidative DNA degradation (5). DNA degradation mediated by bleomycin is metal ion dependent; with the exception of Co·BLM (6), DNA degradation by metallobleomycins also requires oxygen (5,7). It is believed that the degradative event is actually mediated by a ternary complex consisting of bleomycin, a metal ion and oxygen. There are several mechanistically interesting facets of BLM-mediated DNA degradation, including the observed sequence selectivity for 5’-GT-3’ sequences (7–9) and the fact that double-strand cleavage occurs at a frequency greater than that expected from the random accumulation of single-strand breaks (10,11).

Keywords

Squamous Cell Carcinoma Malignant Lymphoma Ternary Complex Degradative Event Random Accumulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Sidney M. Hecht
    • 1
  1. 1.Departments of Chemistry and BiologyUniversity of VirginiaCharlottesvilleUSA

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