Proceedings of the National Academy of Sciences · 1978 · 300 citations · 21 references
MedicineMolecular BiologyOncologyCancer PharmacologyChemotherapyDna RepairAntitumor AntibioticsDna ChemistryDna DamageDna Double-strand Break RepairDna Strand BreaksSingle-strand Break RepairDna Damage InductionDna Double-strand BreaksDna Single-strand BreaksDouble-strand Dna BreaksDrug-induced Dna DamageSequence-selective CleavageSequence-specific Dna CleavageSingle-strand Dna Breaks
We have investigated the sites of DNA damage by the antitumor antibiotics neocarzinostatin and bleomycin by using a 5'-end-labeled DNA fragment of defined sequence as a substrate. At the high drug concentrations used here, neocarzinostatin creates single-strand breaks in DNA at positions of adenine and thymine in the presence of 2-mercaptoethanol, and bleomycin cleaves DNA at GC and GT sequences and to a lesser extent at TA sequences with its degradative activity enhanced by 2-mercaptoethanol. In the presence of ferrous ions, bleomycin cleaves DNA at TT, AT, and TA, as well as at GC and GT sequences. Both antibiotics make double-strand breaks in DNA at specific sites and it is likely that these result from two independent single-strand breaks at nearby sites on opposite strands of the DNA.
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New antibiotics, bleomycin A and B.
Hitoshi Umezawa, Kazuhiko Maeda, Tsutomu Takeuchi et al. · PubMed · 1966 · 732 citations