8oxodG

8oxodG, short for 8-oxo-2'-deoxyguanosine (also written 8-oxo-dG), is a DNA lesion arising from oxidative modification of guanine. It is one of the most frequently studied forms of oxidative DNA damage and serves as a common marker of cellular oxidative stress. The lesion can form directly in DNA or result from the incorporation of oxidized deoxynucleotide triphosphates, such as 8-oxodGTP, during DNA replication.

Formation and mutagenicity: Reactive oxygen species generated during cellular metabolism or environmental exposures attack guanine at the C8 position, yielding 8-oxoG. In a replication context, 8-oxoG can mispair with adenine, potentially causing G:C to T:A transversions if not repaired, contributing to mutagenesis and genomic instability.

DNA repair: The primary repair pathway for 8-oxoG is base excision repair. The enzyme OGG1 glycosylase recognizes and excises 8-oxoG when it is paired with cytosine. If 8-oxoG is opposite adenine, MUTYH glycosylase removes the mispaired A to prevent fixation of mutations. The resulting abasic site is processed by downstream BER enzymes, and the correct base is inserted.

Measurement and significance: 8oxodG is used as a biomarker of oxidative stress and aging. It is measured in DNA or in body fluids such as urine or plasma, using methods like high-performance liquid chromatography with electrochemical detection or liquid chromatography–tandem mass spectrometry. Results can be affected by sample handling, requiring careful protocols.

Clinical and biological relevance: Elevated 8-oxoG/8oxodG levels have been reported in aging, cancer, neurodegenerative and inflammatory diseases, and in responses to environmental and lifestyle factors. The lesion represents a link between oxidative damage and mutational risk.