Kinsella T J, Dobson P P, Mitchell J B
Int J Radiat Oncol Biol Phys. 1986 Aug;12(8):1519-22. doi: 10.1016/0360-3016(86)90207-5.
An in vitro model using Chinese hamster V79 cells was designed to test the interaction of iododeoxyuridine (IdUrd) and its primary metabolite, iodouracil (IU) on growth and radiation response. A recent clinical pharmacology study documented that while steady-state arterial plasma levels of IdUrd remained linear over the dose range of 250-1200 mg/m2/12 hour intravenous infusion, plasma levels of IU rose to greater than 1 log higher (approaching 10(-4) M) at the completion of the 12-hour infusion. Using these clinically relevant doses of IdUrd and IU, we report no apparent effect on radiosensitization of IU alone, or in combination with IdUrd using exponentially growing V79 cells. Similarly, IU does not result in any growth delay. Thus, unlike the recent reports of 5-fluorouracil being incorporated into DNA following phosphorylation to FdUMP, iodouracil does not appear to follow similar metabolic pathways and is unlikely to contribute to the clinical radiosensitizing potential of iododeoxyuridine.
设计了一种使用中国仓鼠V79细胞的体外模型，以测试碘脱氧尿苷（IdUrd）及其主要代谢产物碘尿嘧啶（IU）对生长和辐射反应的相互作用。最近一项临床药理学研究表明，虽然在250 - 1200 mg/m²/12小时静脉输注的剂量范围内，IdUrd的稳态动脉血浆水平保持线性，但在12小时输注结束时，IU的血浆水平上升超过1个对数单位（接近10⁻⁴ M）。使用这些与临床相关的IdUrd和IU剂量，我们报告单独使用IU或与IdUrd联合使用时，对指数生长的V79细胞的放射增敏没有明显影响。同样，IU不会导致任何生长延迟。因此，与最近关于5-氟尿嘧啶磷酸化生成FdUMP后掺入DNA的报道不同，碘尿嘧啶似乎不遵循类似的代谢途径，也不太可能对碘脱氧尿苷的临床放射增敏潜力有贡献。
