ATPase activity of P-glycoprotein related to emergence of drug resistance in Ehrlich ascites tumor cell lines

Thomas Litman*, Dorte Nielsen, Torben Skovsgaard, Thomas Zeuthen, Wilfred D. Stein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

We have characterized the ATPase activity of a sensitive and five progressively daunorubicin resistant Ehrlich ascites tumor cell lines passaged in mice. For the nine different modulators of drug resistance that we have studied, the ATPase activity first rose with the modulator concentration and then declined. We analyzed the ATPase activity profiles in terms of an activation constant and an inhibition constant for each of the nine drugs and six cell lines. In this series of cell lines, the drug-stimulatable ATPase activity was directly proportional to the amount of P-glycoprotein. Pumping of daunorubicin was also correlated with the amount of P-glycoprotein, except that, for a highly passaged line more daunorubicin was pumped than could be accounted for by the content of P-glycoprotein. Between the 12th and the 36th passage an additional source of resistance emerged, which was not correlated with P-glycoprotein. Pumping of daunorubicin was negatively correlated with the cell volume for the different lines.

Original languageEnglish
Pages (from-to)147-158
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1361
Issue number2
DOIs
StatePublished - 22 Aug 1997

Keywords

  • ATPase
  • Daunorubicin
  • Ehrlich tumor
  • Multidrug resistance
  • P-glycoprotein

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