Oxidized DNA (8-oxoG)

Oxidized DNA refers to deoxyribonucleic acid that has sustained chemical modifications, most notably the formation of 8-oxoguanine (8-oxoG), due to the action of reactive oxygen species (ROS) (Cooke et al., 2003). These lesions are highly mutagenic because 8-oxoG can mispair with adenine during replication, leading to G:C to T:A transversions, which are common drivers of oncogenesis (Valavanidis et al., 2009). In healthy cells, these lesions are primarily managed by the base excision repair (BER) pathway, where enzymes like 8-oxoguanine glycosylase (OGG1) recognize and remove the damaged base. From a therapeutic perspective, oxidized DNA is targeted indirectly through the inhibition of repair enzymes (e.g., OGG1 inhibitors like TH5487) to treat inflammatory diseases or through the inhibition of sanitization enzymes like MTH1 to induce lethal DNA damage in cancer cells (Visnes et al., 2018; Gad et al., 2014). Additionally, the presence of oxidized DNA products, such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine or plasma, serves as a critical biomarker for systemic oxidative stress and disease progression (Valavanidis et al., 2009). Targeting the pathways that process oxidized DNA offers a strategy for synthetic lethality in tumors that already possess high baseline levels of oxidative stress.

Other names

8-oxoguanine8-hydroxy-2'-deoxyguanosine8-OHdGOxidative DNA damageDNA lesions8-oxodG

Inhibition of base excision repair (BER) enzymes to prevent the removal of lesions, inhibition of nucleotide pool sanitization (MTH1) to force incorporation of oxidized bases, or use of antioxidants to prevent lesion formation.