Measurement and meaning of oxidatively-modified DNA lesions in urine.

Background: Oxidatively generated damage to DNA has been implicated in the pathogenesis of a wide variety of diseases. The non-invasive assessment of such damage, i.e. in urine, and application to large-scale human studies, is vital to understanding this role, and devising intervention strategies. Methods: We have reviewed the literature in order to establish the status-quo with regard the methods and meaning of measuring DNA oxidation products in urine. Results: Most of the literature focuses upon 8-oxo-7,8-dihydro-2’-deoxyguanosine (8- oxodG), and whilst a large number of these reports concern clinical conditions, there remains (i) lack of consensus between methods, (ii) possible contribution from diet and/or cell death, (iii) no definitive DNA repair source of urinary 2’-deoxyribonucleoside lesions, and (iv) no reference ranges for healthy or diseased individuals. Conclusions: The origin of 8-oxodG is not identified, however recent cell culture studies suggest that the action of Nudix hydrolase(s) on oxidative modification of the nucleotide pool is a likely candidate for the 8-oxodG found in urine and, potentially, of other oxidised 2’- deoxyribonucleoside lesions. Literature reports suggest that diet and cell death have minimal, if any, influence upon urinary levels of 8-oxodG and 8-oxo-7,8-dihydroguanine (8-oxoGua), although this should be assessed on a lesion-by-lesion basis. Broadly speaking, there is consensus between chromatographic techniques, however, ELISA approaches continue to over-estimate 8-oxodG levels and is not sufficiently specific for accurate quantification. With increasing numbers of lesions being studied, it is vital that these fundamental issues are addressed. We report the formation of the European Standards Committee on Urinary (DNA) Lesion Analysis (ESCULA) whose primary goal is to achieve consensus between methods and establish reference ranges in health and disease.