DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity

Natur und Landschaft in der Volksmusik

TIB: RO 433 (1985,4) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Carotenoid intake and supplementation in cancer pro and con

The aim of this review is to summarize the literature data concerning statistical correlations between carotenoid intake and cancer and to provide evidence, if any, that can justify carotenoid supplementation in protocols designed for the prevention and the treatment of cancer diseases. Particular attention will be drawn to lung cancer because of its surprisingly high incidence in cigarette smokers and asbestos workers who received high doses of beta-carotene. The efficacy of carotenoids and retinol as adjuvants in the therapeutic procedures against cancer and the clinical indications for carotenoid supplementation will be discussed

Clinical Use of Carotenoids - Antioxidative Protection Versus Prooxidative Side Effects.

Carotenoids are natural pigments, which are found in bacteria, algae, fungi and plants, but which are not synthesized in animals. Animals and human beings get carotenoids through food. If we think on carotenoids, we think mostly on ?-carotene, lycopene, lutein, zeaxanthin, and some others. But, meanwhile 600 to 700 carotenoids were identified. About 60 of them are components of our nutrition. Almost ten percent of all carotenoids in mammals can be metabolized to retinol, which is vitamin A, and can therefore function as vitamin A precursors. Carotenoids and retinoids act as antioxidants, influence the growth of the organism, immunological functions, the visual cycle, and modulate gene expression, too. Epidemiological data have strongly linked higher levels of carotenoid intake and increased circulating and tissue concentrations of carotenoids with reduced risk for various cancers, cardiovascular disease, and other diseases, even clinical intervention trials did not find homogeneous and significant evidence, that ?-carotene alone leads to these benefits. In contrast to expectations and to the medical benefits induced by high intake of carotenoids by nutrition and via supplements in heavy smokers and asbestos workers the incidence and mortality in lung carcinoma even increased in high-dosage ?-carotene supplementation. These observations initiated research projects with the aim, to find out the cause of potential toxic effects of high-dosage ?-carotene supplementation. Obviously, the toxic effects can be attributed oxidative breakdown products of ?-carotene and other carotenoids. The previous results argue for toxic effects only at high-dosage supplementation in heavy smokers and asbestos workers, i.e. under conditions of severe oxidative stress. From in vitro experiments was concluded, that even at very high carotenoid concentration a toxic effect towards biomolecules can be avoided if the other components of the antioxidative network are present at high levels