8-Oxo-dGTP

8-Oxo-dGTP (8-Oxo-Deoxyguanosine triphosphate) is an oxidized guanine nucleotide formed by ROS-mediated oxidative modification of dGTP, and it also serves as a key substrate for 8-oxo-dGTP pyrophosphohydrolases (such as hMTH1 and E. coli MutT). 8-Oxo-dGTP acts as a DNA mutagen, inserts into nascent DNA and pairs with adenine and cytosine, inducing A:T to C:G transversion mutations. Furthermore, 8-Oxo-dGTP causes oxidative DNA base modification, strand breakage and S-phase arrest, and ultimately triggers AIF-mediated apoptosis and promotes spontaneous carcinogenesis in mth1-deficient mice. Accumulation of 8-Oxo-dGTP in cells induces genomic instability, but it exhibits a tumor-suppressive effect that reduces tumor incidence in mouse models instead. 8-Oxo-dGTP is widely used in studies related to spontaneous carcinogenesis, Parkinson's disease, Alzheimer's disease, heart failure and tumor mechanisms^[1][2][3][4]. In Vitro: 8-Oxo-dGTP (100 μM) binds to wild-type hMTH1 with high affinity (K_d=0.08 μM), while the F27A and D119A mutations reduce the binding affinity, and the W117A mutation completely abolishes the binding activity^[1].
8-Oxo-dGTP (2-8 mM; 24 h) inhibits the viability of HeLa-shGFP and HeLa-shMTH1 cells in a dose-dependent manner, with the inhibitory effects at concentrations of 6 mM and 8 mM being stronger than that of 50 μg/mL 5-FU^[4].
8-Oxo-dGTP (2 mM, 6 mM; 8-24 h) increases the level of 8-oxo-dG in DNA of HeLa-shGFP cells in a dose- and time-dependent manner, and this elevation reaches comparable levels in HeLa cells with MTH1, OGG1 or MUTYH knockdown after 24 h of treatment^[4].
8-Oxo-dGTP (6 mM; 24 h) induces S-phase cell cycle arrest in HeLa-shGFP and HeLa-shMTH1 cells, with a more pronounced effect in MTH1-knockdown HeLa cells; treatment with 6 mM 8-oxo-dGTP for 12 h also induces S-phase arrest in double thymidine-synchronized HeLa-shGFP and HeLa-shMTH1 cells^[4].
8-Oxo-dGTP (2 mM, 6 mM; 24 h) induces apoptosis in HeLa-shGFP, HeLa-shMTH1, HeLa-shOGG1 and HeLa-shMUTYH cells via an AIF-mediated caspase-independent pathway, which is evidenced by elevated levels of cleaved PARP and nuclear translocation of AIF^[4]. In Vivo: 8-oxo-dGTP (0.5 mg/kg; intravenous injection; once every 10 days; for 17 months) reduces the spontaneous tumor incidence rate to 19.4% in MTH1 knockout mice and to 14.7% in wild-type mice after 17 months of administration^[4].
8-oxo-dGTP (0.5 mg/kg; intravenous injection; once every 3 days; for 32 consecutive days) inhibits the growth of subcutaneous HeLa-shMTH1 xenografts in nude mice^[4].
8-oxo-dGTP (0.5-2.5 mg/kg; intravenous injection; once every 5 days; for 112 consecutive days) dose-dependently inhibits spontaneous intestinal adenoma formation^[4].