Nitroxides block DNA scission and protect cells from oxidative damage

Journal Article · Tue Jan 01 00:00:00 EST 1991 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00216a033· OSTI ID:5527181

Samuni, A; Godinger, D; Aronovitch, J ^[1]; Russo, A; Mitchell, J ^[2]

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1. Hebrew Univ., Jerusalem (Israel)
2. National Institutes of Health, Bethesda, MD (USA)

The protective effect of cyclic stable nitroxide free radicals, having SOD-like activity, against oxidative damage was studied by using Escherichia coli xthA DNA repair-deficient mutant hypersensitive to H{sub 2}O{sub 2}. Oxidative damage induced by H{sub 2}O{sub 2} was assayed by monitoring cell survival. The metal chelator 1,10-phenanthroline (OP), which readily intercalates into DNA, potentiated with H{sub 2}O{sub 2}-induced damage. The extent of in vivo DNA scission and degradation was studied and compared with the loss of cell viability. The extent of DNA breakage correlated with cell killing, supporting previous suggestions that DNA is the crucial cellular target of H{sub 2}O{sub 2} cytotoxicity. The xthA cells were protected by catalase but not by superoxide dismutase (SOD). Both five- and six-membered ring nitroxides, having SOD-like activity, protected growing and resting cells from H{sub 2}O{sub 2} toxicity, without lowering H{sub 2}O{sub 2} concentration. To check whether nitroxides protect against O{sub 2}{sup {center dot}{minus}}-independent injury also, experiments were repeated under hypoxia. These nitroxides also protected hypoxic cells against H{sub 2}O{sub 2}, suggesting alternative modes of protection. Since nitroxides were found to reoxidize DNA-bound iron(II), the present results suggest that nitroxides protect by oxidizing reduced transition metals, thus interfering with the Fenton reaction.

• OSTI ID: 5527181
• Journal Information: Biochemistry; (USA), Vol. 30:2; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ESCHERICHIA COLI
CELL KILLING
NITROGEN OXIDES
BIOLOGICAL EFFECTS
STRAND BREAKS
DNA REPAIR
ELECTRON SPIN RESONANCE
HYDROGEN PEROXIDE
NITROXYL RADICALS
PHENANTHROLINES
SUPEROXIDE DISMUTASE
AROMATICS
AZAARENES
BACTERIA
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CHALCOGENIDES
ENZYMES
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
MAGNETIC RESONANCE
MICROORGANISMS
NITROGEN COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDES
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEROXIDES
RADICALS
RECOVERY
REPAIR
RESONANCE
550201* - Biochemistry- Tracer Techniques