Iron(II)-bleomycin. Biochemical and spectral properties in the presence of radical scavengers

Luis O. Rodriguez, Sidney M. Hecht

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Abstract

Consistent with a recent literature report (Repine, J. E. etal. (1981) Proc.Nat.Acad.Sci.USA7̄8̄, 1001-1003), the release of [3H]-thymine from PM-2 DNA by Fe(II)-H2O2-generated ·OH was suppressed by dimethyl sulfoxide. In contrast, DMSO did not affect [3H]-thymine release mediated by Fe(II)-bleomycin. Under aerobic conditions in the presence of t-butyl phenylnitrone, Fe(II)-BLM produces an epr signal that has been presumed to arise by transfer of ·OH or O2 from the "active complex" of bleomycin to the spin trap. Remarkably, high concentrations (80 mM) of PBN had no effect on the ability of Fe(II)-BLM to solubilize [3H]-thymine, although the ability of authentic ·OH to degrade DNA was completely suppressed under these condition. The suproxide dismutase catalyst tetrakis(4-N-methylpyridyl)porphineiron(III) also failed to suppress BLM-mediated DNA degradation. Moreover, the epr signal observed with 1.6 mM Fe(II)-BLM in the presence of 80 mM PBN was found to be much less intense than that produced by 1.6 mM Fe(II) and 290 mM H2O2, but equivalent in intensity to that obtained with 45 mM Fe(II) and exoess H2O2. We conclude that the fragmentation of DNA produced by Fe(II)-BLM can be due neither to free ·OH nor to O2. We suggest that DNA degradation is initiated by an "active complex" consisting of BLM, metal and oxygen that functions by abstracting H· from susceptible sites on DNA.

Original languageEnglish (US)
Pages (from-to)1470-1476
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume104
Issue number4
DOIs
StatePublished - Feb 26 1982

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ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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