ESTIMATION OF OXIDATIVE DNA-DAMAGE IN MAN FROM URINARY-EXCRETION OF REPAIR PRODUCTS

DNA is constantly damaged and repaired in living cells. The repair pro ducts of the oxidative DNA lesions, i.e. oxidised nucleosides and base s, are poor substrates for the enzymes involved in nucleotide synthesi s, are fairly water soluble, and generally excreted into the urine wit hout further metabolism. Among the possible products, 8-oxo-2'-deoxygu anosine, 8-oxoguanine, thymine glycol, thymidine glycol and, 5-hydroxy methyluracil have so far been identified in urine. It should be emphas ised that the excretion of the repair products in urine represents the average rate of damage in the total body whereas the level of oxidise d bases in nuclear DNA is a concentration measurement in that specific tissue/cells in the moment of sampling. The rate of oxidative DNA mod ifications has been studied in humans by means of the repair products as urinary biomarkers, particularly with respect to 8-oxo-2'-deoxyguan osine. The data obtained so far indicate that the important determinan ts of the oxidative damage rate include tobacco smoking, oxygen consum ption 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. f rom cruciferous vegetables.The data are consistent with the experiment ally based notion that oxidative DNA damage is an important mutagenic and apparently carcinogenic factor. However, the proof of a causal rel ationship in humans is still warranted. In the future the use of bioma rkers may provide this evidence and allow further investigations on th e qualitative and quantitative importance of oxidative DNA modificatio n and carcinogenesis in man, as well as elucidate possible preventive measures.