Benson A B, Trump D L, Cummings K B, Fischer P H
Biochem Pharmacol. 1985 Nov 1;34(21):3925-31. doi: 10.1016/0006-2952(85)90446-0.
Iododeoxyuridine (IdUrd) potentiated the lethal but not the growth inhibitory properties of fluorouracil (FUra) and fluorodeoxyuridine (FdUrd) in human bladder cancer cells (T24). The rate of incorporation of IdUrd into DNA was enhanced by both fluoropyrimidines, but to a significantly greater extent by FdUrd. Both inhibition of iododeoxyridylate dehalogenation and the depletion of thymidine triphosphate pools contributed to the increased incorporation rate. Inhibition of dehalogenation accounted for 67% of the observed stimulation in the case of FUra, but only 37% of the increase produced by FdUrd. The depletion of dTTP pools, both in the presence and absence of IdUrd, was greater after FdUrd than FUra exposure. The observed increase in the rate of incorporation of IdUrd appears to account for the enhanced toxicity seen with FdUrd, but other factors may be involved in the case of FUra. Since FUra and IdUrd appear to be mutually potentiating and do not share a dependence on thymidine kinase activity, this drug combination warrants further investigation.
碘脱氧尿苷（IdUrd）增强了氟尿嘧啶（FUra）和氟脱氧尿苷（FdUrd）对人膀胱癌细胞（T24）的致死性而非生长抑制特性。两种氟嘧啶均增强了IdUrd掺入DNA的速率，但FdUrd的增强程度明显更大。碘脱氧嘧啶核苷酸脱卤作用的抑制和三磷酸胸苷池的消耗均导致掺入率增加。在FUra的情况下，脱卤作用的抑制占观察到的刺激作用的67%，但在FdUrd产生的增加中仅占37%。无论有无IdUrd，FdUrd暴露后dTTP池的消耗均比FUra暴露后更大。观察到的IdUrd掺入率的增加似乎解释了FdUrd所见的增强毒性，但在FUra的情况下可能涉及其他因素。由于FUra和IdUrd似乎相互增效且不依赖胸苷激酶活性，这种药物组合值得进一步研究。
