
handle: 10146/17397
3.1. Biomarkers of DNA base oxidation 3.2. Lipid peroxidation induced DNA damage Free radical attack upon DNA generates, among other changes, modified bases. The amount of 8-oxo-7,8-dihydroguanine, one of the most critical lesions in human lymphocytes, was found to be 1.2/106. Gua by a mass spectrometric approach. Spurious oxidation occurring during sample preparation is the major problem in measurement of oxidised bases in DNA. Exposure to ambient air particles and benzene is associated with higher levels of 8-oxo-7,8-dihydroguanine and other oxidatively modified bases. Studies of the effects of antioxidant supplements and antioxidant-rich food have given contradictory results. New techniques allowing the simultaneous determination of 8-oxo-7,8-dihydro-2’-deoxyguanosine, 8-oxo-7,8-dihydroguanine and 5-methylhydroxy-uracil in urine samples have revealed that the combined amount of these compounds excreted into urine of healthy human subjects corresponds to about 2800 oxidative modifications of guanine per cell per day. Cohort studies are required to assess whether an increased level of biomarkers of oxidative DNA damage is associated with an increased risk of developing cancer. Lipid peroxidation resulting from chronic inflammatory processes can result in production of excess reactive oxygen and reactive nitrogen species and DNA-reactive aldehydes, including 4-hydroxy-2-nonenal, malonaldehyde, acrolein, and crotonaldehyde. Alkylation of DNA bases by these reactive electrophiles is thought to contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced lipid peroxidation. The specific and sensitive methods developed for the detection of these potentially mutagenic adducts in human tissues and in urine have been applied to the analysis of DNA from a variety of normal and disease-related samples. ECNIS Network of Excellence
oxidation, lipid, DNA, damage
oxidation, lipid, DNA, damage
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