Abstract
Oxidatively generated damage to DNA has been implicated in the pathogenesis of a wide variety of diseases. The noninvasive assessment of such damage, i.e., in urine, and application to large-scale human studies are vital to understanding this role and devising intervention strategies. We have reviewed the literature to establish the status quo with regard to the methods and meaning of measuring DNA oxidation products in urine. Most of the literature focus upon 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and whereas a large number of these reports concern clinical conditions, there remains (a) lack of consensus between methods, (b) possible contribution from diet and/or cell death, (c) no definitive DNA repair source of urinary 2'-deoxyribonucleoside lesions, and (d) no reference ranges for healthy or diseased individuals. 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 oxidized 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, although this should be assessed on a lesion-by-lesion basis. Broadly speaking, there is consensus between chromatographic techniques; however, ELISA approaches continue to overestimate 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 whose primary goal is to achieve consensus between methods and establish reference ranges in health and disease.
Highlights
Reactive oxygen species (ROS) are produced continually, from normal cellular metabolism, but may be produced in excess, leading to oxidative stress, following exposure to xenobiotics, radiation etc
Methods of analysis For the most part, methods that have been applied to the analysis of oxidatively damaged DNA lesions in urine are either chromatographic, or immunoassay
Using HPLC, Tg that was termed a ‘significant marker’ of oxidative stress [21], was one of the first ROS-induced DNA lesions to be studied in urine
Summary
Reactive oxygen species (ROS) are produced continually, from normal cellular metabolism, but may be produced in excess, leading to oxidative stress, following exposure to xenobiotics, radiation etc. This approach was first applied to the simultaneous analysis of five urinary, oxidatively modified DNA base products including 8-oxoGua, 5-HMUra, 5-hydroxyuracil (5-OHUra), 8-oxodG, and 8-oxo-7,8-dihydroadenine (8-oxoAde); [31].
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.