Adaptation of mouse leukemia cells L1210 to vincristine. Evidence for expression of P-glycoprotein

Neoplasma. 1992;39(2):73-7.

Abstract

A vincristine resistant cell line was obtained from mouse leukemia cells L1210 by long-term adaptation in a medium with stepwise increasing concentrations of vincristine. By Western blotting using monoclonal antibody C219, positive signal on the presence of P-glycoprotein was observed in the resistant cells. Moreover, hybridization of mRNA from vincristine resistant cells with radiolabeled MDR1 cDNA probe gave evidence about the expression of MDR1 gene. The observed resistance may be depressed by application of "chemosensitizers" such as (1) calcium entry blockers (verapamil and nifedipine); (2) neuroleptics (trifluorperasine) and (3) local anesthetics (lidocaine) directly to the grow medium. Any significant effect in O2 consumption as well as incorporation of [U-14C]-glucose by the sensitive or resistant cells was not detected in the absence of vincristine. Presence of vincristine induced increasing velocity of O2 consumption by resistant cells from 2.5 +/- 0.3 to 3.3 +/- 0.2 microliters/min.10(6) cells, and, on the other hand, decreasing O2 consumption by sensitive cells from 2.3 +/- 0.2 to 1.7 +/- 0.1 ml/min.10(6) cells. The presence of vincristine induced less potent decrease in glucose incorporation by resistant cells in comparison with values which were observed in sensitive cells.

Publication types

  • Comparative Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Adaptation, Biological / physiology*
  • Animals
  • Cell Survival / drug effects
  • Culture Media
  • Drug Resistance
  • Energy Metabolism / drug effects
  • Glucose / metabolism
  • Intracellular Fluid / metabolism
  • Kinetics
  • Leukemia L1210 / drug therapy*
  • Leukemia L1210 / metabolism
  • Leukemia L1210 / physiopathology
  • Membrane Glycoproteins / physiology*
  • Mice
  • Oxygen Consumption / drug effects
  • Sensitivity and Specificity
  • Tumor Cells, Cultured / drug effects
  • Vincristine / pharmacology*
  • Vincristine / toxicity

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Culture Media
  • Membrane Glycoproteins
  • Vincristine
  • Glucose