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Ferritin enhances production of DNA strand breaks by 6-hydroxydopamine, ascorbic acid and H2O2 in CCC PM2 bacteriophage DNA

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Abstract

Damage of CCC PM2 DNA by 6-hydroxydopamine (6-OHDA) and ascorbic acid (AA), compounds that are both able to release iron from ferritin, was significantly enhanced in the presence of ferritin. H2O2, a product of 6-OHDA autoxidation, did not induce DNA strand breaks in the absence of ferritin and only to a minor extent in the presence of ferritin. DNA damage by 6-OHDA and AA could be reduced by the hydroxyl radical scavenger mannitol, the iron chelator desferrioxamine, and, partly, by a combination of superoxide dismutase and catalase. These inhibitory effects were clearly less pronounced in the presence of ferritin. Ferritin obviously played an important role as a source of iron in the pro-oxidative processes of 6-OHDA and AA. These features might be of importance in cancer therapy since many tumor cells contain elevated ferritin levels.

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References

  • Aronovitch J, Godinger D, Samuni A, Czapski G. 1987 Ascorbic acid oxidation and DNA scission catalyzed by iron and copper chelates.Free Rad Res Commun 2, 241–258.

    Google Scholar 

  • Blakely WF, Fuciarelli AF, Wegher BJ, Dizdaroglu M. 1990 Hydrogen peroxide-induced base damage in deoxyribonucleic acid.Radiat Res 121, 338–343.

    PubMed  Google Scholar 

  • Boyer RF, McCleary CJ. 1987 Superoxide ion as a primary reductant in ascorbate-mediated ferritin iron release.Free Rad Biol Med 3, 389–395.

    PubMed  Google Scholar 

  • Boyer RF, Clark HM, LaRoche AP. 1988 Reduction and release of ferritin iron by plant phenolics.J Inorg Biochem 32, 171–181.

    PubMed  Google Scholar 

  • Bruchelt G, Schraufstätter, IU, Niethammer D, Cochrane CG. 1991 Ascorbic acid enhances the effects of 6-hydroxydopamine and H2O2 on iron-dependent DNA strand breaks and related processes in the neuroblastoma cell line SK-N-SH.Cancer Res 51, 6066–6072.

    PubMed  Google Scholar 

  • Heikkila R, Cohen G. 1972 Further studies on the generation of hydrogen peroxide by 6-hydroxydopamine. Potentiation by ascorbic acid.Mol Pharmacol 8, 241–248.

    PubMed  Google Scholar 

  • Iancu TC. 1989 Iron and neoplasia: ferritin and hemosiderin in tumor cells.Ultrastruct Pathol 13, 573–584.

    PubMed  Google Scholar 

  • Jackson JH, Schraufstätter IU, Hyslop PA et al. 1987 Role of oxidants in DNA damage. Hydroxyl radical mediates the synergistic DNA damaging effects of asbestos and cigarette smoke.J Clin Invest 80, 1090–1095.

    PubMed  Google Scholar 

  • Kobayashi, S, Yoshida K, Ueda K, Sakai H, Komano T. 1988 DNA damage caused by ascorbate in the presence of Cu2+ induces mutations.Nucleic Acids Symp Ser 19, 29–32.

    PubMed  Google Scholar 

  • Lode HN, Bruchelt G, Rieth AG, Niethammer D. 1990 Release of iron from ferritin by 6-hydroxydopamine under aerobic and anaerobic conditions.Free Rad Res Commun 11, 153–158.

    Google Scholar 

  • Loeb LA, James EA, Waltersdorph AM, Klebanoff SJ. 1988 Mutagenesis by the autoxidation of iron with isolated DNA.Proc Natl Acad Sci USA 85, 3918–3922.

    PubMed  Google Scholar 

  • Lown JW. 1984 Ethidium binding assay for reactive oxygen species generated from reductively activated adriamycin (doxorubicin).Methods Enzymol 105, 532–539.

    PubMed  Google Scholar 

  • Monteiro HP, Winterbourn CC. 1989a 6-Hydroxydopamine releases iron from ferritin and promotes ferritin-dependent lipid peroxidation.Biochem Pharmacol 38, 4177–4182.

    PubMed  Google Scholar 

  • Monteiro HP, Winterbourn CC. 1989b Release of iron from ferritin by divicine, isouramil, acid-hydrolyzed vicine, and dialuric acid and initiation of lipid peroxidation.Arch Biochem Biophys 271, 536–545.

    PubMed  Google Scholar 

  • O'Connell MJ, Peters TJ. 1987 Ferritin and haemosiderin in free radical generation, lipid peroxidation and protein damage.Chem Phys Lipids 45, 241–249.

    PubMed  Google Scholar 

  • Reynolds CP, Reynolds DA, Frenkel EP, Smith RG. 1982 Selective toxicity of 6-hydroxydopamine and ascorbate for human neuroblastomain vitro: a model for clearing marrow prior to autologous transplant.Cancer Res 42, 1331–1336.

    PubMed  Google Scholar 

  • Sachs C, Jonsson G. 1975. Mechanisms of action of 6-hydroxydopamine.Biochem Pharmacol 24, 1–8.

    PubMed  Google Scholar 

  • Samokyszyn VM, Thomas CE, Reif DW, Saito M, Aust SD. 1988 Release of iron from ferritin and its role in oxygen radical toxicities.Drug Metab Rev,19, 283–303

    PubMed  Google Scholar 

  • Schneider JE, Browning MM, Floyd RA. 1988 Ascorbate/iron mediation of hydroxyl free radical damage to PBR322 plasmid DNA.Free Rad Biol Med 5, 287–295.

    PubMed  Google Scholar 

  • Slivka A, Cohen G. 1985 Hydroxyl radical attack on dopamine.J Biol Chem 260, 15466–15472.

    PubMed  Google Scholar 

  • Theil EC. 1987 Ferritin: structure, gene regulation, and cellular function in animals, plants, and microorganisms.Annu Rev Biochem 56, 289–315.

    PubMed  Google Scholar 

  • Winterbourn CC, Vile GF, Monteiro HP. 1991 Ferritin, lipid peroxidation and redox-cycling xenobiotics.Free Rad Res Commun 12/13, 107–114.

    Google Scholar 

  • Wolley PV, Kumar S, Fitzgerald P, Simpson RT. 1987 Ascorbate potentiates DNA damage by 1-methyl-1-nitrosoureain vivo and generates DNA strand breaksin vitro.Carcinogenesis 8, 1657–1662.

    PubMed  Google Scholar 

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Rieth, A.G., Baader, S.L., Lode, H.N. et al. Ferritin enhances production of DNA strand breaks by 6-hydroxydopamine, ascorbic acid and H2O2 in CCC PM2 bacteriophage DNA. Biometals 5, 223–227 (1992). https://doi.org/10.1007/BF01061222

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  • DOI: https://doi.org/10.1007/BF01061222

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