8-Oxo-dGTP  (Synonyms: 8-Oxo-Deoxyguanosine triphosphate)

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].

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

523.18

C₁₀H₁₆N₅O₁₄P₃

139307-94-1

O[C@H]1C[C@H](N2C(N=C(N)NC3=O)=C3N=C2O)O[C@@H]1COP(OP(OP(O)(O)=O)(O)=O)(O)=O

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Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Sakai Y, et al. A molecular basis for the selective recognition of 2-hydroxy-dATP and 8-oxo-dGTP by human MTH1. J Biol Chem. 2002;277(10):8579-8587.  [Content Brief]

  [2]. Bialkowski K, et al. A novel assay of 8-oxo-2′-deoxyguanosine 5′-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) activity in cultured cells and its use for evaluation of cadmium (II) inhibition of this activity[J]. Nucleic acids research, 1998, 26(13): 3194-3201.

  [3]. Tsutsui H, et al. 8-oxo-dGTPase, which prevents oxidative stress-induced DNA damage, increases in the mitochondria from failing hearts. Circulation. 2001;104(24):2883-2885.  [Content Brief]

  [4]. Li J, et al. 8-oxo-dGTP curbs tumor development via S phase arrest and AIF-mediated apoptosis. Free Radic Biol Med. 2023;196:53-64.  [Content Brief]