Tezuka M, Sugiyama H, Tamemasa O, Inaba M
Gan. 1982 Feb;73(1):70-6.
A 5-fluorouracil (5-FU)-resistant cell line of P388 mouse leukemia was established by intraperitoneal treatment with the drug. The activities of enzymes responsible for the formation of 5-fluoro-2'-deoxyuridine 5'-monophosphate and 5-fluorouridine 5'-monophosphate from 5-FU, the quantities of 5-FU metabolites, and the permeability to 5-FU were determined in both the 5-FU-sensitive and the resistant cell lines. It was found that the activities of uridine kinase and uracil phosphoribosyltransferase, the initial uptake of 5-FU, and the intracellular levels of 5-FU-nucleotides were all decreased in the resistant cells. However, the initial uptake of 5-FU into cells preincubated with KCN was the same in the sensitive and the resistant cells. These results support the view that the ineffectiveness of 5-FU against the resistant cell line of P388 leukemia can be attributed to decreases in the activities of enzymes responsible for the formation of 5-FU-nucleotides and probably also decreased transport of 5-FU in the resistant cells.
通过腹腔注射5-氟尿嘧啶（5-FU）建立了P388小鼠白血病的5-FU耐药细胞系。测定了5-FU敏感和耐药细胞系中负责从5-FU形成5-氟-2'-脱氧尿苷5'-单磷酸和5-氟尿苷5'-单磷酸的酶活性、5-FU代谢产物的量以及对5-FU的通透性。结果发现，耐药细胞中尿苷激酶和尿嘧啶磷酸核糖基转移酶的活性、5-FU的初始摄取以及5-FU核苷酸的细胞内水平均降低。然而，用KCN预孵育的细胞对5-FU的初始摄取在敏感细胞和耐药细胞中是相同的。这些结果支持这样一种观点，即5-FU对P388白血病耐药细胞系无效可归因于负责5-FU核苷酸形成的酶活性降低，并且可能还归因于耐药细胞中5-FU的转运减少。
