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HU (100 μm), significantly increased the phosphorylation of 3TC in HepG2 cells, with significant reductions in dCTP also noted at this concentration. The resulting 3TCTP/dCTP ratio was increased dramatically. The mechanism behind this interaction involves the production of dCTP itself. dCTP is produced from two sources, the reduction of circulating cytidine-DP (CDP) to form dCDP, which is then phosphorylated to dCTP (the de novo pathway), and, the sequential phosphorylation of dC to dCTP (the dC salvage pathway).
| Cell Experiment | |
|---|---|
| Cell lines | HepG2 cell |
| Preparation method | Extracts were stored at −20°C until determination of dCTP pools by a similar procedure to that described previously. Reaction mixtures (100 μl) contained 0.2μCi [3H]-dATP, 0.25 μm synthetic oligonucleotide primer, 10 mm MgCl2, 5 mm dithiothreitol, 50 mm Tris-HCl (pH 7.5) and 1 unit Sequenase 2.0 enzyme. |
| Concentrations | -- |
| Incubation time | 24 h |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | |
| Dosages | |
| Administration | |
| Molecular Weight | 467.16 |
| Formula | C9H16N3O13P3 |
| CAS Number | 2056-98-6 |
| Solubility (25°C) | 10mM in DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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