8-hydroxy-2'-deoxyguanosine (8-OHdG)

8-hydroxy-2'-deoxyguanosine (8-OHdG) is a major product of oxidative DNA damage and serves as a critical biomarker for oxidative stress within the cell. It is formed by the reaction of hydroxyl radicals with the guanine base in DNA, leading to a lesion that can cause G:C to T:A transversion mutations if not properly repaired by the base excision repair (BER) pathway, primarily via the enzyme 8-oxoguanine glycosylase (OGG1). Beyond its role as a mutagenic lesion, 8-OHdG acts as a damage-associated molecular pattern (DAMP), capable of triggering innate immune responses through the cGAS-STING and TLR9 pathways, thereby linking oxidative stress to chronic inflammation. In clinical and pharmacological contexts, 8-OHdG is widely utilized as a non-invasive biomarker for monitoring oxidative damage in diseases such as cancer, diabetes, and neurodegeneration. Therapeutic strategies targeting 8-OHdG include the development of OGG1 inhibitors, which aim to exploit the high oxidative stress levels in cancer cells by preventing the repair of these lesions, ultimately leading to genomic instability and cell death. Additionally, MTH1 inhibitors are being explored to prevent the incorporation of oxidized dGTP into the DNA of rapidly dividing tumor cells, representing a novel approach to targeted cancer therapy.

Other names

8-oxo-7,8-dihydro-2'-deoxyguanosine8-oxodGOxidized deoxyguanosineDNA-OHOH-DNA

Drugs targeting 8-OHdG typically act by inhibiting the enzymes responsible for its repair (e.g., OGG1 inhibitors) to induce lethal DNA damage in cancer cells, or by inhibiting the sanitization of the nucleotide pool (e.g., MTH1 inhibitors) to prevent its incorporation into genomic DNA. Conversely, antioxidants act by scavenging reactive oxygen species (ROS) to prevent the formation of 8-OHdG.