在移植性大鼠肿瘤和三个正常大鼠组织的体外研究中，研究了肌苷对氧茄嘧啶诱导的5-氟尿嘧啶（FUra）活化抑制的影响。以小肠和詹森肉瘤为基础，通过确定在相同的孵育条件下FUra标记为14C-放射性的核糖核酸（RNA）纯化物的摄取量，评估了RNA活性。氧茄嘧啶将FUra并入肠道RNA的能力最多降低93％，但仅抑制约45％的肿瘤RNA摄取FUra。在存在足够的氧茄嘧啶以引起大约这些水平的抑制时，肌苷未能刺激小肠RNA中FUra的摄取，而0.1毫摩尔的肌苷将Jensen肉瘤RNA中的FUra摄取恢复到无氧茄嘧啶对照水平，并且0.5毫摩尔的肌苷将FUra 摄取提高了29％以上的对照水平。两种组织的酶解肌苷的能力几乎相等。考虑到氧茄嘧啶的作用机制和肌苷的代谢目前正在了解，这些结果表明，在我们的体外条件下，大鼠小肠无法利用来自肌苷的核糖-1-磷酸刺激将FUra转化为5-氟脲苷酸（FUMP），而詹森肉瘤有效地利用这种来自肌苷的核糖-1-磷酸来源从FUra增加FUMP的产量。在无氧茄嘧啶的情况下，肌苷将Jensen肉瘤总RNA中的FUra的摄取增加了57％，与无肌苷对照组相比，但显著抑制了小肠总RNA中的FUra的摄取。

The effects of inosine on oxipurinol-induced inhibition of 5-fluorouracil (FUra) activation were investigated in a transplantable rat tumor and three normal rat tissues in vitro. FUra activation directed toward RNA was assessed in preparations of small intestine and Jensen sarcoma by determining the uptake of 14C-labeled FUra into purified total RNA of each tissue under identical conditions of incubation. Oxipurinol reduced the incorporation of FUra into intestinal RNA by as much as 93% but inhibited FUra uptake into tumor RNA by only about 45%. In the presence of sufficient oxipurinol to induce inhibition at approximately these levels, inosine failed to stimulate FUra uptake into intestinal RNA, whereas 0.1 mM inosine restored FUra uptake into Jensen sarcoma RNA to the level found in oxipurinol-free controls, and 0.5 mM inosine increased FUra uptake 29% above the controls. Both tissues had a nearly equivalent enzymatic capacity to cleave inosine by phosphorolysis. In view of what is currently known about the mechanism of action of oxipurinol and the metabolism of inosine, these results suggested that under our in vitro conditions rat small intestine was incapable of utilizing ribose-1-phosphate derived from inosine to stimulate the conversion of FUra to 5-fluorouridylate (FUMP), whereas Jensen sarcoma efficiently used this source of ribose-1-phosphate to increase the production of FUMP from FUra. In the absence of oxipurinol, inosine increased FUra uptake into total RNA of Jensen sarcoma by as much as 57%, compared to inosine-free controls, but markedly inhibited FUra uptake into total RNA of the small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)