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Etheno DNA adducts as critical exposure markers: quantification and mutational specificity in experimental systems and man

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Potential biomarkers for environmental exposure and nutritionally derived oxidative stress

Exposure of cells to persistent oxidative stress is capable of causing excessive injury through mutation. Quantification of the DNA damage can be used to estimate critical levels of tissue tolerance before the development of malignancies.

Health

Oxidative stress can be induced after exposure of cells in various environmental conditions such as UV and ionizing radiation or chemicals, but it can also be a result of natural biochemical processes like lipid metabolism. Cells can suffer excessive damage from modifications to their compartments and very often to their genetic material, the DNA molecules. Most cells have evolved antioxidant mechanisms that consist of two components: specific enzymes such as catalase and antioxidant substances like vitamins. Under normal conditions, the cells can cope with the free radicals that are produced during the cell metabolism. The oxidative stress and the subsequent damage starts when the balance between the oxidants and the antioxidants is disturbed and the inborn mechanisms are not enough to protect the cell from the free radicals produced either from internal or from external factors. The most serious damage caused by the oxidative stress is on the DNA molecules. Increased concentrations of free radicals in the cell environment can change the normal chemical structure of the nucleoside bases that the DNA consists of, producing abnormal bonds called etheno adducts. Etheno adducts are highly mismatching spots in the double helix of DNA that can cause specific point mutations that are thought to be responsible in triggering carcinogenic and ageing processes. Researchers in Germany have used known chemical carcinogens to imitate the reaction of tissues to oxidative stress and have developed a method to measure the etheno adducts in healthy and treated tissues. They have found that there is a “background” number of etheno adducts that are the result of normal metabolism and probably accumulates with age. Dietary habits can increase the number of those “background” DNA adducts, as can some chronic infections or inflammatory processes. There was also a correlation between the etheno adducts in cell DNA and the genetic changes produced after treatment. It is believed that continuous exposure of cells to oxidative stress can initiate malignancies through DNA damage and mutation. The number of DNA etheno adducts seems to be a representative marker of this procedure and can prove helpful in the prevention and treatment of human cancers. More extensive population studies are needed in order to correlate low biomarker levels and nutritional profiles, helping us to establish critical levels of oxidative stress exposure.

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