DNA-breaking versus DNA-protecting activity of four phenolic compounds in vitro.
Given the paradoxical effects of phenolics in oxidative stress, we evaluated the relative pro-oxidant and antioxidant properties of four natural phenolic compounds in DNA nicking. The phenolic compounds differed dramatically in their ability to nick purified supercoiled DNA, with the relative DNA nicking activity in the order: 1,2,4-benzenetriol (100% nicking) > gallic acid > caffeic acid > gossypol (20% nicking). Desferrioxamine (0.02 mM) decreased DNA strand breakage by each phenolic, most markedly with gallate (85% protection) and least with caffeic acid (26% protection). Addition of metals accelerated DNA nicking, with copper more effective (approximately 5-fold increase in damage) than iron with all four phenolics. Scavengers revealed the participation of specific oxygen-derived active species in DNA breakage. Hydrogen peroxide participated in all cases (23-90%). Hydroxyl radicals were involved (32-85%), except with 1,2,4-benzenetriol. Superoxide participated (81-86%) with gallic acid and gossypol, but not with caffeic acid or 1,2,4-benzenetriol. With 1,2,4-benzenetriol, scavengers failed to protect significantly except in combination. Thus, in the presence of desferrioxamine, catalase or superoxide dismutase inhibited almost completely. When DNA breakage was induced by Fenton's reagent (ascorbate plus iron) the two catechols (caffeic acid and gossypol) were protective, whereas the two triols (1,2,4-benzenetriol and gallic acid) exacerbated damage.
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Bioenergetics Research Laboratory, Faculty of Applied Sciences, Simon Fraser University, Burnaby, BC, Canada.
Bandy
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Tsang
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Davison
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D000975:Antioxidants / Q000737:chemistry*; D001205:Ascorbic Acid / Q000737:chemistry; D002109:Caffeic Acids / Q000737:chemistry; D002614:Chelating Agents / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D004249:DNA Damage; D004278:DNA, Superhelical / Q000737:chemistry*; D003676:Deferoxamine / Q000737:chemistry; D004587:Electrophoresis, Agar Gel; D016166:Free Radical Scavengers / Q000737:chemistry; D005707:Gallic Acid / Q000737:chemistry; D006072:Gossypol / Q000737:chemistry; D006873:Hydroquinones / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D009153:Mutagens / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry*; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry*
D000975:Antioxidants; D002109:Caffeic Acids; D002614:Chelating Agents; D004278:DNA, Superhelical; D016166:Free Radical Scavengers; D006873:Hydroquinones; D009153:Mutagens; D016877:Oxidants; D010636:Phenols; C013038:hydroxyhydroquinone; D005707:Gallic Acid; D003300:Copper; D007501:Iron; D003676:Deferoxamine; D006072:Gossypol; D001205:Ascorbic Acid; C040048:caffeic acid