DNA repair is responsible for the presence of oxidatively damaged DNA lesions in urine.
The repair of oxidatively damaged DNA is integral to the maintenance of genomic stability, and hence prevention of a wide variety of pathological conditions, such as aging, cancer and cardiovascular disease. The ability to non-invasively assess DNA repair may provide information regarding repair pathways, variability in repair capacity, and susceptibility to disease. The development of assays to measure urinary DNA lesions offered this potential, although it rapidly became clear that possible contribution from diet and cell turnover may influence urinary lesion levels. Whilst early studies attempted to address these issues, up until now, much of the data appears conflicting. However, recent work from our laboratories, in which human volunteers were fed highly oxidatively modified 15N-labelled DNA demonstrates that diet does not appear to contribute to urinary levels of 8-hydroxyguanine and 7,8-dihydro-8-oxo-2'-deoxyguanosine. Furthermore, we propose that a number of literature reports form an argument against a contribution from cell death. Indeed we, and others, have presented evidence, which strongly suggests the involvement of cell death to be minimal. Taken together, these data would appear to rule out various confounding factors, leaving DNA repair pathways as the principal source of urinary purine, if not DNA, lesions enabling such measurements to be used as indicators of repair.
Cooke
Marcus S
MS
Department of Cancer Studies and Molecular Medicine, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester LE2 7LX, UK. msc5@le.ac.uk
Evans
Mark D
MD
Dove
Rosamund
R
Rozalski
Rafal
R
Gackowski
Daniel
D
Siomek
Agnieszka
A
Lunec
Joseph
J
Olinski
Ryszard
R
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D016923:Cell Death; D004247:DNA / Q000652:urine*; D004249:DNA Damage; D004260:DNA Repair; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D004032:Diet; D006147:Guanine / Q000031:analogs & derivatives* / Q000652:urine*; D006801:Humans; D008954:Models, Biological; D018384:Oxidative Stress; D051381:Rats
C024829:8-hydroxyguanine; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine