Estimation of oxidative DNA damage in man from urinary excretion of repair products.
DNA is constantly damaged and repaired in living cells. The repair products of the oxidative DNA lesions, i.e. oxidised nucleosides and bases, are poor substrates for the enzymes involved in nucleotide synthesis, are fairly water soluble, and generally excreted into the urine without further metabolism. Among the possible products, 8-oxo-2'-deoxyguanosine, 8-oxoguanine, thymine glycol, thymidine glycol and, 5-hydroxymethyluracil have so far been identified in urine. It should be emphasised that the excretion of the repair products in urine represents the average rate of damage in the total body whereas the level of oxidised bases in nuclear DNA is a concentration measurement in that specific tissue/cells in the moment of sampling. The rate of oxidative DNA modifications has been studied in humans by means of the repair products as urinary biomarkers, particularly with respect to 8-oxo-2'-deoxyguanosine. The data obtained so far indicate that the important determinants of the oxidative damage rate include tobacco smoking, oxygen consumption and some inflammatory diseases whereas diet composition, energy restriction and antioxidant supplements have but a minimal influence, possibly with the exception of yet unidentified phytochemicals, e.g. from cruciferous vegetables. The data are consistent with the experimentally based notion that oxidative DNA damage is an important mutagenic and apparently carcinogenic factor. However, the proof of a causal relationship in humans is still warranted. In the future the use of biomarkers may provide this evidence and allow further investigations on the qualitative and quantitative importance of oxidative DNA modification and carcinogenesis in man, as well as elucidate possible preventive measures.
Department of Pharmacology, University of Copenhagen, Denmark. steffen.loft@farmakol.ku.dk
S
S
Loft
H E
HE
Poulsen
D000970:Antineoplastic Agents / Q000009:adverse effects; D015415:Biomarkers / Q000652:urine; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D009705:Nucleosides / Q000652:urine*; D009711:Nucleotides / Q000652:urine*; D010084:Oxidation-Reduction; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D000970:Antineoplastic Agents; D015415:Biomarkers; D009705:Nucleosides; D009711:Nucleotides