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.
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- CAS No.: 139307-94-1
- Formula: C10H16N5O14P3
- Molecular Weight:523.18
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
8-Oxo-dGTP (100 μM) binds to wild-type hMTH1 with high affinity (Kd=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.
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Cell Line:HeLa-shGFP, HeLa-shMTH1
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Concentration:2 mM, 4 mM, 6 mM, 8 mM
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Incubation Time:8 h， 16 h， 24 h
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Result:Inhibited cell viability in a dose-dependent manner in both HeLa-shGFP and HeLa-shMTH1 cells.
Showed higher inhibition rates at 6 mM and 8 mM than the positive control 5-FU (50 μg/mL).
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Cell Line:HeLa-shGFP, HeLa-shMTH1, HeLa-shOGG1, HeLa-shMUTYH
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Concentration:2 mM, 6 mM
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Incubation Time:24 h
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Result:Induced apoptosis in a dose-dependent manner in HeLa-shGFP and HeLa-shMTH1 cells, with a higher percentage of apoptotic cells in HeLa-shMTH1 cells.
Did not alter the apoptotic response in cells with knockdown of OGG1 or MUTYH.
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Cell Line:HeLa-shGFP, HeLa-shMTH1, HeLa-shOGG1, HeLa-shMUTYH
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Concentration:2 mM, 6 mM
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Incubation Time:24 h
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Result:Increased cleaved PARP levels in all tested cell lines.
Decreased cytoplasmic AIF levels and increased nuclear AIF levels in all tested cell lines.
Caused no significant changes to classical caspase-dependent pathway proteins (Bcl-2, Bax, Cyto-c, caspase-3).
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.
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Animal Model:C57/6J-ApcMin/Nju mice with Spontaneous intestinal adenoma (male and female; 4 weeks old; fed 60% high-fat diet to induce intestinal polypoid tumors)[4]
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Dosage:0.5 mg/kg; 2.5 mg/kg
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Administration:i.v.; every 5 days; 112 days
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Result:Reduced average intestinal polypoid tumor count to 23 per mouse, with a tumor number inhibition rate of 38% at 0.5 mg/kg.
Reduced average intestinal polypoid tumor count to 15 per mouse, with a tumor number inhibition rate of 58% at 2.5 mg/kg.
Most efficiently inhibited tumor growth across all diameter categories (<2 mm, 2-4 mm, >4 mm) at 2.5 mg/kg.
Chemical Information
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CAS No. 139307-94-1
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Molecular Weight 523.18
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Formula C10H16N5O14P3
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SMILES
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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Synonyms
8-Oxo-Deoxyguanosine triphosphate
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Initial Source
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[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]
[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]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
8-Oxo-dGTP Related Classifications
HY-112817 Related Classifications
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