Effects of inhibitors of arachidonic acid metabolism and vitamin E on oxygen radical-induced sister chromatid exchanges

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Abstract
Oxidative damage to membranes initiates lipid peroxidation chain reactions and stimulation of the arachidonic acid cascade. The products of these reactions may mediate the genetic toxicity of oxygen radicals. Arachidonic acid alone induced sister chromatid exchange (SCE) formation and significantly augmented the genetic damage observed with an oxygen radical-generating system. The number of SCEs was reduced significantly in oxygen radical-treated Chinese hamster ovary cells incubated wtih inhibitors of the cyclo-oxygenase and lipoxygenase pathways. Vitamin E, when combined with inhibitors of arachidonic acid metabolism, protected target cells completely from oxygen radical-induced genotoxicity. These data support the hypothesis that lipid peroxidation intermediates may be involved in the genesis of radical-generated genetic lesions.

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