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Iron requirement for cellular DNA damage and growth inhibition by hydrogen peroxide and bleomycin. Biochem J 1994 Sep 15;302 ( Pt 3)(Pt 3):655-64

Date

09/15/1994

Pubmed ID

7524474

Pubmed Central ID

PMC1137281

DOI

10.1042/bj3020655

Scopus ID

2-s2.0-0028136871 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

Studies with Euglena gracilis and HL-60 cells have assessed the need for intracellular iron in the mechanisms of inhibition of cell growth and DNA damage by H2O2 and bleomycin. Cell culture media were directly depleted of iron in order to deprive cells of nutrient iron. Major pools of cellular iron were reduced in both cell types. Nevertheless, iron bound in e.s.r.-observable haem protein and ribonucleotide diphosphate reductase in HL-60 cells was not decreased. In both control cell populations, there was a concentration-dependent reduction in proliferation and cell survival caused by H2O2. In comparison, the proliferation rates of both iron-deficient cell types were significantly less sensitive to H2O2. H2O2 caused concentration-dependent single-strand breakage in DNA in control HL-60 and Euglena gracilis cells. Iron deficiency reduced the amount of strand breaks in HL-60 cells at each concentration of H2O2 used. Single-strand breakage caused by H2O2 in Euglena gracilis was a direct function of the concentration of iron in which the cells had been grown. Growth inhibition and both single- and double-strand DNA damage caused by bleomycin were substantially reduced or eliminated in iron-deficient cells. Copper bleomycin behaved like metal-free bleomycin when assayed for the capacity to cause DNA damage in iron-normal and iron-deficient HL-60 cells. In contrast, iron bleomycin was equally active under the two conditions in these cells.

Author List

Radtke K, Lornitzo FA, Byrnes RW, Antholine WE, Petering DH



MESH terms used to index this publication - Major topics in bold

Animals
Binding Sites
Bleomycin
Cell Division
Cell Survival
DNA Damage
Dose-Response Relationship, Drug
Electron Spin Resonance Spectroscopy
Euglena gracilis
Hydrogen Peroxide
Iron
Tumor Cells, Cultured