8-Oxo-2'-deoxyguanosine

8-Oxo-2'-deoxyguanosine

8-Oxo-2'-deoxyguanosine (8-oxo-dG) is a modified nucleoside that results from the oxidative damage of DNA. It is one of the most common products of DNA oxidation and serves as a biomarker for oxidative stress and DNA repair processes.

Structure and Formation

8-Oxo-2'-deoxyguanosine is formed when the guanine base in DNA is oxidized to 8-oxoguanine. This modification can occur due to reactive oxygen species (ROS) generated during normal cellular metabolism or from external sources such as radiation and pollution. The presence of 8-oxo-dG in DNA can lead to mutations if not repaired, as it can mispair with adenine during DNA replication.

Biological Significance

The presence of 8-oxo-dG in DNA is a marker of oxidative stress, which is implicated in various diseases, including cancer, neurodegenerative diseases, and aging. Cells have evolved repair mechanisms, such as the base excision repair pathway, to remove 8-oxo-dG and prevent mutagenesis.

Detection and Measurement

8-Oxo-2'-deoxyguanosine can be detected and quantified using various techniques, including high-performance liquid chromatography (HPLC) coupled with electrochemical detection, mass spectrometry, and immunoassays. These methods are used in research to study oxidative stress and the efficacy of antioxidants.

Role in Disease

The accumulation of 8-oxo-dG is associated with the pathogenesis of several diseases. In cancer, oxidative DNA damage can lead to mutations that drive tumorigenesis. In neurodegenerative diseases, oxidative stress contributes to neuronal damage and cell death. Monitoring 8-oxo-dG levels can provide insights into disease mechanisms and the effectiveness of therapeutic interventions.

DNA Demethylation and 8-Oxo-dG

8-Oxo-2'-deoxyguanosine is also involved in the process of DNA demethylation. During active demethylation, 8-oxo-dG can be generated as an intermediate. This process is crucial for the regulation of gene expression and epigenetic modifications.

Related Pages

• DNA repair
• Oxidative stress
• Base excision repair
• Reactive oxygen species

Gallery

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  Colonic epithelium mouse without tumorigenesis (A) and with tumorigenesis (B). Brown shows 8-oxo-dG.
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  Initiation of DNA demethylation at a CpG site.
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  Demethylation of 5-methylcytosine.

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  Colonic epithelium mouse without tumorigenesis (A) and with tumorigenesis (B). Brown shows 8-oxo-dG.
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  Initiation of DNA demethylation at a CpG site.
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  Demethylation of 5-methylcytosine.