Properties and products of the degradation of dna by bleomycin and iron(II)

Edward A. Sausville, Roland W. Stein, Jack Peisach, Susan Band Horwitz

Research output: Contribution to journalArticle

307 Citations (Scopus)

Abstract

Bleomycin and Fe(II) together act to cause the highly efficient degradation of adenovirus-2 DNA to acid-soluble products when the drug and metal ion are present in a one- to twofold excess of DNA. Where the bleomycin-DNA ratio is less than 1, breakage of DNA occurs to a greater extent than is seen with Fe(II) in the absence of bleomycin. Breakage of DNA occurs from pH 4.5 to greater than 10 and is not greatly dependent on temperature. The appearance of activity between pH 4 and 6 is related to the appearance of a 1:1 Fe(II)-bleomycin complex with λmax 476 nm, εM (apparent) = 3.8 × 102, and pK = 5.2. The reaction proceeds to completion in less than l min at 37°C and requires the presence of molecular oxygen. Increased ionic strength inhibits the reaction. Degradation of DNA by Fe(II)-bleomycin is not inhibited by superoxide dismutase or catalase at high bleomycin concentrations; however, at low concentrations of bleomycin inhibition by superoxide dismutase, but not by catalase, is observed. All four bases in DNA are released by Fe(II)-bleomycin (T > C > A > G). Discrete nuclease-resistant oligonucleotides of average length 7-10 residues are formed in the limit degradation of DNA by Fe(II)-bleomycin. Mononucleotides and inorganic phosphate are not produced. A product which resembles malondialdehyde is found and its formation is maximal at a 1:1 Fe(II) to bleomycin ratio in reactions containing excess DNA. The products of the degradation of DNA by Fe(II)-bleomycin are in accord with the proposal that Fe(II) is the ultimate cofactor of bleomycin in degrading DNA.

Original languageEnglish (US)
Pages (from-to)2746-2754
Number of pages9
JournalBiochemistry
Volume17
Issue number14
StatePublished - 1978

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Degradation
DNA
Bleomycin
Catalase
Superoxide Dismutase
iron bleomycin
Molecular oxygen
Ionic strength
Malondialdehyde
Adenoviridae
Oligonucleotides
Osmolar Concentration
Metal ions
Metals
Phosphates
Ions
Oxygen
Temperature
Acids
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sausville, E. A., Stein, R. W., Peisach, J., & Band Horwitz, S. (1978). Properties and products of the degradation of dna by bleomycin and iron(II). Biochemistry, 17(14), 2746-2754.

Properties and products of the degradation of dna by bleomycin and iron(II). / Sausville, Edward A.; Stein, Roland W.; Peisach, Jack; Band Horwitz, Susan.

In: Biochemistry, Vol. 17, No. 14, 1978, p. 2746-2754.

Research output: Contribution to journalArticle

Sausville, EA, Stein, RW, Peisach, J & Band Horwitz, S 1978, 'Properties and products of the degradation of dna by bleomycin and iron(II)', Biochemistry, vol. 17, no. 14, pp. 2746-2754.
Sausville, Edward A. ; Stein, Roland W. ; Peisach, Jack ; Band Horwitz, Susan. / Properties and products of the degradation of dna by bleomycin and iron(II). In: Biochemistry. 1978 ; Vol. 17, No. 14. pp. 2746-2754.
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