8oxodGTP

8-oxo-dGTP, often written as 8oxodGTP, is an oxidized form of the deoxyguanosine triphosphate pool. It arises when reactive oxygen species oxidize nucleotides in the cellular nucleotide pool. As a substrate for DNA polymerases, 8-oxo-dGTP can be misincorporated into DNA, producing mutagenic lesions that contribute to genomic instability.

The mutagenic potential of 8-oxo-dGTP stems from its tendency to pair incorrectly during replication. When incorporated opposite templated bases, 8-oxo-dGTP can lead to G:C to T:A transversions, a common result of oxidative damage. In addition to mispairing, the lesion can be propagated through subsequent rounds of replication if not repaired, increasing mutation risk.

Cells employ several safeguards to minimize incorporation of oxidized nucleotides. The MutT homolog family, especially human MTH1 (NUDT1), hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP and pyrophosphate, thereby sanitizing the nucleotide pool before incorporation into DNA. If 8-oxoG is incorporated into DNA, base excision repair pathways counteract the damage: MutY glycosylase removes mispaired adenine opposite 8-oxoG, while OGG1 excises 8-oxoG when paired with cytosine.

8-oxo-dGTP is of interest in aging and cancer research. Elevated levels reflect oxidative stress and can correlate with mutagenesis and genomic instability. Inhibitors targeting MTH1 have been explored as potential anticancer strategies, aiming to increase DNA damage selectively in tumor cells with high oxidative stress. Detection and quantification of 8-oxo-dGTP in cells and tissues are performed using techniques such as high-performance liquid chromatography and mass spectrometry.