Abstract

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.