Iron-mediated oxidative DNA damage detected by fluorometric analysis of DNA unwinding in isolated rat liver nuclei.
Studies were performed to determine the extent of nuclear DNA degradation induced by iron, iron-ascorbate, or iron-bleomycin under aerobic conditions in a model system using isolated rat liver nuclei. The effects of five antioxidants (catalase, superoxide dismutase, dimethyl sulfoxide, glutathione and diallyl sulfide) on this oxidative nuclear damage were also investigated. At the 0.05 level for statistical significance, iron induced concentration-dependent DNA degradation, and this effect was enhanced by ascorbate and bleomycin. The antioxidants catalase, dimethyl sulfoxide, and diallyl sulfide significantly reduced the iron-ascorbate-induced DNA damage, whereas superoxide dismutase and dimethyl sulfoxide significantly reduced iron-bleomycin-induced damage. Glutathione significantly increased the iron-bleomycin-induced DNA damage. These results suggest that the reactive oxygen species generated by iron, iron-ascorbate, and iron-bleomycin are responsible for the DNA strand breaks in isolated rat liver nuclei.
Sahu
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Molecular Toxicology Laboratory, Food and Drug Administration, Washington, D.C. 20204.
Washington
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D005470:Fluorometry; D016166:Free Radical Scavengers; D066298:In Vitro Techniques; D007501:Iron / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009690:Nucleic Acid Conformation; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D000975:Antioxidants; D016166:Free Radical Scavengers; D007501:Iron