Characteristics of the vincristine induced augmentation of methotrexate uptake in Ehrlich ascites tumor cells

M. J. Fyfe, I. D. Goldman

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Studies were undertaken to characterize the effect of vincristine on methotrexate uptake in Ehrlich ascites tumor cells and to define the mechanism of this interaction. Vincristine (10 μM) does not alter the unidirectional influx of methotrexate but slows the unidirectional efflux of methotrexate and leads to a large increase in the steady state level of exchangeable intracellular methotrexate. These effects of vincristine are rapidly, but not completely, reversible. Vincristine stimulation of net methotrexate H3 uptake occurs within 4 min of exposure of cells to this agent and increases over an extracellular vincristine concentration range of at least 5 to 50 μM. Vincristine does not alter the intracellular water content nor the chloride distribution ratio. The addition of glucose to the medium partially reverses the effect of vincristine and completely reverses the stimulatory effect of sodium azide on the net uptake of methotrexate. Vincristine (10 μM) increases net uptake of methotrexate in L1210 leukemia cells but does not have a significant effect on net methotrexate uptake in the L cell mouse fibroblast over a 21/2 hour interval of exposure even though replication of the L cell is completely arrested. The similarity between the effects of vincristine and metabolic poisons on methotrexate uptake and the partial reversal of the effect of vincristine by glucose suggest that this agent enhances methotrexate uptake by the inhibition of cellular energy metabolism with the consequent inhibition of an energy dependent process which limits methotrexate accumulation within the cell. The data suggest further that this effect of vincristine represents an interaction with a cellular element(s) that is different from the interaction which results in the arrest of cell division in metaphase.

Original languageEnglish (US)
Pages (from-to)5067-5073
Number of pages7
JournalJournal of Biological Chemistry
Volume248
Issue number14
StatePublished - Dec 1 1973
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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