DNA-Breaking versus DNA-protecting activity of four phenolic compounds in vitro

Given the paradoxical effects of phenolics in oxidative stress, we evaluate d the relative pro-oxidant and antioxidant properties of four natural pheno lic compounds in DNA nicking. The phenolic compounds differed dramatically in their ability to nick purified supercoiled DNA, with the relative DNA ni cking activity in the order: 1,2,4-benzenetriol (100% nicking) > gallic aci d > caffeic acid > gossypol (20% nicking). Desferrioxamine (0.02 mM) decrea sed DNA strand breakage by each phenolic, most markedly with gallate (85% p rotection) and least with caffeic acid (26% protection). Addition of metals accelerated DNA nicking, with copper more effective (similar to5-fold incr ease in damage) than iron with ail four phenolics. Scavengers revealed the participation of specific oxygen-derived active species in DNA breakage. Hy drogen 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 signifi cantly except in combination. Thus, in the presence of desferrioxamine, cat alase or superoxide dismutase inhibited almost completely. When DNA breakag e 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-b enzenetriol and gallic acid) exacerbated damage.