Electrochemical Detection of 8-Hydroxy-2-Deoxyguanosine Levels in Cellular DNA

Oxidative stress has been implicated in the etiology of many pathological states and known to result in
DNA
damage. Oxidative DNA damage can lead to mutagenesis (
1
–
3
) and has been associated with aging (
4
), diabetes mellitus (
5
), inflammatory disease (
1
) and carcinogenesis (
1
–
3
,
6
). The 8-hydroxy-2-deoxyguanosine lesion (8-OHdG) is often used in the assessment of oxidative DNA damage and has become the de facto marker for oxidative damage to DNA. 8-OHdG is one of the most prominent lesions observed following exposure to ionizing radiation (
7
) but also results from treatment with many xenobiotics (
8
) as well as by endogenous mechanisms. Thus, normal endogenous levels becomes a critical issue in the assessment of cellular 8-OHdG levels in pathological states. Furthermore, 8-OHdG is efficiently repaired by a DNA glycosylase specific for this lesion (
9
) and its contribution to mutagenesis is relatively weak (
10
–
12
). However, it is representative of approximately 20 additional oxidatively-denved lesions known to result from radiation damage (
13
) and whose mutagenic outcome are largely unknown in mammalian-cell systems.