Liposoluble antioxidants provide an effective radioprotective barrier

Ionising radiation causes the massive generation of reactive oxygen species and induces cellular DNA damage. The antioxidant, protective effects of several compounds against gamma-ray-induced chromosomal damage were determined by the micronucleus test, evaluating the reduction in the frequency of micronuclei in cytokinesis-blocked human lymphocytes. The compounds studied were added to human blood at 25 microM, 5 min before or after irradiation with 2 Gy of caesium-137. The results suggest that different protective mechanisms are operating in each case. When the phenolic compounds are added before gamma-irradiation, their protective antimutagenic activity is based on their scavenging capacity against superoxide anion (O(2)(.-)) and, especially, hydroxyl radical ((.)OH), regardless of whether they are oil- or water-soluble compounds. When the phenolic compounds are added after gamma-irradiation treatment, the protective effect relies on activity against reactive oxygen species present in cells, i.e. lipoperoxy radicals (R(-)OO(.)), which are mainly responsible for continuous chromosomal oxidative damage. In addition, ionising radiation enhances lysosomal enzyme secretion and arachidonate release from membranes through lipo-oxygenase, cyclo-oxygenase and phospholipase activities, thus increasing the inflammatory cell response. Only oil-soluble compounds, such as carnosic acid, carnosol and delta-tocopherol, provide a significant protective antimutagenic activity. The most powerful water-soluble antioxidants lack the capacity to protect against gamma-ray-induced damage. The difference between anti-radical and anti-lipoperoxidant activities could explain the different behaviour of the compounds tested in terms of protecting against the lipid peroxidative processes. This anti-lipoperoxidant activity depends on several factors, but it is clear that only the lipo-antioxidants are effective in protecting human cells against oxidative damage, even when administered after exposure to ionising radiation.