BIOCHEMICAL CHARACTERISTICS OF A 5-FLUOROURACIL-RESISTANT SUBLINE OF P388 LEUKEMIA

  • 1 January 1982
    • journal article
    • research article
    • Vol. 73  (1) , 70-76
Abstract
A 5-fluorouracil(5-FU)-resistant cell line of P388 mouse leukemia was established by i.p. 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 the 5-FU-sensitive and the resistant cell lines. 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. The initial uptake of 5-FU into cells preincubated with KCN was the same in the sensitive and the resistant cells. 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.