MULTIDRUG-RESISTANCE OF MURINE LEUKEMIA-CELLS - CHARACTERIZATION AND CORRELATION WITH CYTOCHROME-P-450 DEPENDENT ACTIVITIES, CYTOSOLIC CALCIUM AND CELL-CYCLE STATE

This paper reports studies on P388 leukemic cells sensitive and resist ant to ADR and VCR. The P450 dependent enzyme system and the cytosolic calcium were estimated and are discussed in relation to MDR. It could be shown, in comparison to sensitive P388 cells, that the plasma memb rane permeability for fluorescent dyes like rhodamine 123 and fura-2 a nd the biotransformation of xenobiotics are changed in resistant cells . Whereas the transport behaviour for the dyes is similarly induced in resistant cells independent of the drug which made the MDR, the P450 dependent enzyme activities are strongly increased in P388/ADR in comp arison to the P388 and P388/VCR. The cell cycle analysis shows the sam e effect. Many mor e cells of P388/ADR are in the S-phase in compariso n to P388 or P388/VCR. The LI is also increased in this direction. The refore, it can be concluded that, depending on the kind of drug which made the MDR, different biochemical mechanisms are activated.