Cell killing and DNA damage by hydrogen peroxide are mediated by intracellular iron. (2024)

PMCID: PMC1153333

A C Mello Filho, M E Hoffmann, and R Meneghini

Copyright and License information PMC Disclaimer

Abstract

Phenanthroline, a strong iron chelator, prevents both the formation of DNA single-strand breaks and the killing of mouse cells produced by H2O2. These results, taken together with our previous findings, indicate that the DNA damage is produced by hydroxyl radicals formed when H2O2 reacts with chromatin-bound Fe2+ and that this damage is responsible for the killing effect.

• Borek C, Troll W. Modifiers of free radicals inhibit in vitro the oncogenic actions of x-rays, bleomycin, and the tumor promoter 12-O-tetradecanoylphorbol 13-acetate. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1304–1307. [PMC free article] [PubMed] [Google Scholar]
• Dooley MM, Pryor WA. Free radical pathology: inactivation of human alpha-1-proteinase inhibitor by products from the reaction of nitrogen dioxide with hydrogen peroxide and the etiology of emphysema. Biochem Biophys Res Commun. 1982 Jun 15;106(3):981–987. [PubMed] [Google Scholar]
• Fridovich I. Superoxide dismutases. Annu Rev Biochem. 1975;44:147–159. [PubMed] [Google Scholar]
• Gutteridge JM, Rowley DA, Halliwell B. Superoxide-dependent formation of hydroxyl radicals and lipid peroxidation in the presence of iron salts. Detection of 'catalytic' iron and anti-oxidant activity in extracellular fluids. Biochem J. 1982 Sep 15;206(3):605–609. [PMC free article] [PubMed] [Google Scholar]
• Halliwell B. Superoxide-dependent formation of hydroxyl radicals in the presence of iron salts is a feasible source of hydroxy radicals in vivo. Biochem J. 1982 Aug 1;205(2):461–463. [PMC free article] [PubMed] [Google Scholar]
• Hoffmann ME, Meneghini R. Action of hydrogen peroxide on human fibroblast in culture. Photochem Photobiol. 1979 Jul;30(1):151–155. [PubMed] [Google Scholar]
• McCord JM. Free radicals and inflammation: protection of synovial fluid by superoxide dismutase. Science. 1974 Aug 9;185(4150):529–531. [PubMed] [Google Scholar]
• Meneghini R. Gaps in DNA synthesized by ultraviolet light-irradiated WI38 human cells. Biochim Biophys Acta. 1976 Apr 2;425(4):419–427. [PubMed] [Google Scholar]
• Meneghini R, Hoffmann ME. The damaging action of hydrogen peroxide on DNA of human fibroblasts is mediated by a non-dialyzable compound. Biochim Biophys Acta. 1980 Jun 27;608(1):167–173. [PubMed] [Google Scholar]
• Moody CS, Hassan HM. Mutagenicity of oxygen free radicals. Proc Natl Acad Sci U S A. 1982 May;79(9):2855–2859. [PMC free article] [PubMed] [Google Scholar]
• Repine JE, Fox RB, Berger EM. Hydrogen peroxide kills Staphylococcus aureus by reacting with staphylococcal iron to form hydroxyl radical. J Biol Chem. 1981 Jul 25;256(14):7094–7096. [PubMed] [Google Scholar]
• Siesjö BK, Rehncrona S, Smith D. Neuronal cell damage in the brain: possible involvement of oxidative mechanisms. Acta Physiol Scand Suppl. 1980;492:121–128. [PubMed] [Google Scholar]
• Simon RH, Scoggin CH, Patterson D. Hydrogen peroxide causes the fatal injury to human fibroblasts exposed to oxygen radicals. J Biol Chem. 1981 Jul 25;256(14):7181–7186. [PubMed] [Google Scholar]
• Tolmasoff JM, Ono T, Cutler RG. Superoxide dismutase: correlation with life-span and specific metabolic rate in primate species. Proc Natl Acad Sci U S A. 1980 May;77(5):2777–2781. [PMC free article] [PubMed] [Google Scholar]