Oxidative cell wall damage mediated by bleomycin-Fe(II) in Saccharomyces cerevisiae.
Bleomycin mediates cell wall damage in the yeast Saccharomyces cerevisiae. Bleomycin treatments in the presence of Fe(II) increased the rate of spheroplast formation by lytic enzymes by 5- to 40-fold. Neither Fe(III) nor other tested ions caused significant cell wall damage in the presence of bleomycin. The effect of bleomycin-Fe(II) on the cell wall mimicked the characteristics of bleomycin-Fe(II)-mediated DNA damage in dependence on aeration, inhibition by ascorbate, and potentiation by submillimolar concentrations of sodium phosphate. Bleomycin-mediated cell wall damage was time and dose dependent, with incubations as short as 20 min and drug concentrations as low as 3.3 x 10(-7)M causing measurable cell wall damage in strain CM1069-40. These times and concentrations are within the range of effectiveness for bleomycin-mediated DNA damage and for the cytotoxicity of the drug. Although Fe(III) was inactive with bleomycin and O2, the bleomycin-Fe(III) complex damaged walls and lysed cells in the presence of H2O2. H2O2 causes similar activation of bleomycin-Fe(III) in assays of DNA scission. These results suggest that an activated bleomycin-Fe-O2 complex disrupts essential cell wall polymers in a manner analogous to bleomycin-mediated cleavage of DNA.
Lim
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ST
Department of Biological Sciences, Hunter College of the City University of New York, New York 10021, USA.
Jue
C K
CK
Moore
C W
CW
Lipke
P N
PN
D001761:Bleomycin / Q000494:pharmacology* / Q000031:analogs & derivatives; D002473:Cell Wall / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology*; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D013104:Spheroplasts / Q000187:drug effects; D013997:Time Factors
C023503:iron bleomycin; D001761:Bleomycin; D006861:Hydrogen Peroxide; D007501:Iron