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

Nitrogen uptake strategies of edaphically specialized Bornean tree species

The association of tree species with particular soil types contributes to high b diversity in forests, but the mechanisms producing such distributions are still debated. Soil nitrogen (N) often limits growth and occurs in differentially available chemical forms. In a Bornean forest where tree species composition changes dramatically along a soil gradient varying in supplies of different N-forms, we investigated whether tree species’ N-uptake and soil specialization strategies covaried. We analyzed foliar 15N natural abundance for a total of 216 tree species on clay or sandy loam (the soils at the gradient’s extremes) and conducted a 15N-tracer experiment with nine specialist and generalist species to test whether species displayed flexible or differential uptake of ammonium and nitrate. Despite variation in ammonium and nitrate supplies and nearly 4 % difference in foliar δ15N between most soil specialists and populations of generalists on these soils, our 15N tracer experiment showed little support for the hypothesis that soil specialists vary in N-form use or the ratios in which they use these forms. Instead, our results indicate that these species possess flexible capacities to take up different inorganic N forms. Variation between soil specialists in uptake of different N forms is thus unlikely to cause the soil associations of tree species and high b diversity characteristic of this Bornean rain forest. Flexible uptake strategies would facilitate N-acquisition when supply rates of N-forms exhibit spatiotemporal variation and suggest that these species may be functionally redundant in their responses to N gradients and influences on ecosystem N-cycles