Effects of arachidonic acid and inhibitors of arachidonic acid metabolism on phagocyte-induced sister chromatid exchanges.

Stimulated human phagocytes produce toxic oxygen radicals which induce sister chromatid exchanges in cultured mammalian cells. 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 significantly augmented the number of sister chromatid exchanges in target cells exposed to stimulated phagocytes. This genetic damage was abrogated in radical-treated cells preincubated with inhibitors of the cyclooxygenase (indomethacin), lipoxygenase (nordihydroguaiaretic acid) or both (piroxicam) pathways.