Determination of DNA damage by analysis of oxidized nucleosides and their use as biomarkers

A. Wagner, G. Jahreis, Jena

Reactive oxygen species are continuously produced in the cells by endogenous and exogenous processes. Hydroxyl radicals are the most reactive oxygen species. Due to an inadequate antioxidative defence against the ROS, damage to the DNA may occur. In animal experiments, oxidative DNA damage has been shown to be an important factor in cancerogenesis.

As oxidative damages are not completely eliminated, damaged nucleosides accumulate with growing age. Repair products of the oxidative damage are excreted with the urine. The most frequent DNA mutation - and DNA damage of utmost mutagenicity - is 8-oxo-2'-deoxyguanosine (8-oxodG). The oxidized DNA bases and nucleosides are used as biomarkers of the extent of DNA damage. They indicate the rate of damage in specific target organs or the repair rate of DNA modifications excreted with the urine. A direct correlation exists between the 8-oxodG excretion rate and metabolic activity, a main source of endogenous oxidative stress. The results of various studies on the effects of restricted energy supply and antioxidant supplementation have been inconsistent. Available data confirm that a diet rich in fruit and vegetables reduces the concentration of 8-oxodG in the urine. A low-fat diet, furthermore, reduces the concentration of 5-hydroxymethyl-uracil in the leukocytes, another biomarker of oxidative stress. Oxidative DNA modifications are also examined as biomarkers with regard to various diseases and types of cancer. Keywords: DNA damage / oxidative stress / 8-oxo-2'-deoxyguanosine Sie finden den Artikel in deutscher Sprache in Ernährungs-Umschau 05/04 ab Seite 178.

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