Conjugated Dienes and TBA Reactive Material as Components of Chromosome Breakage Factors
Clastogenic components have been described as so-called chromosome breakage factors or “clastogenic factors ” (CF) as an indirect effect of ionizing radiation. They have been also observed in the hereditary breakage syndromes Ataxia telangiectasia and Bloom’ s syndrome, in chronic inflammatory diseases and in supernatants of cell cultures exposed to the tumor promoter phorbol-myristate-acetate (PMA) or to a superoxide generating xanthine-xanthine oxidase system. The formation and action mechanisms of CF are intimely linked to the generation of superoxide anion radicals, since superoxide dismutase can prevent their formation and their chromosome damaging effect. However, the observation that the clastogenic material is transferable from one culture system to the other cannot be understood by short-lived free radicals. Oxygen radicals and other oxidants appear to be toxic in large part because they initiate the chain reaction of lipid peroxidation in membranes. Oxidative damage to membranes may be at the origin of the clastogenic material called CF by formation of lipid hydroperoxides and fragmentation products. According to this hypothesis, we have examined the supernatants of lymphocyte cultures for the presence of lipid peroxidation products. These cell cultures had been exposed to PMA or a xanthine-xanthine oxidase reaction which represent two in vitro model systems: The PMA induced CF may serve as a model for CF in chronic inflammatory diseases, and the induction of CF by xanthine-xanthine oxidase reaction may be a model for the oxidative damage observed in the phenomenon of ischemia/reperfusion injury.
KeywordsXanthine Oxidase Chronic Inflammatory Disease Lipid Peroxidation Product Lymphocyte Culture Arachidonic Acid Cascade
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