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 resistant 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 membrane permeability for fluorescent dyes like rhodamine 123 and fura-2 and 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 comparison to the P388 and P388/VCR. The cell cycle analysis shows the same effect. Many more cells of P388/ADR are in the S-phase in comparison to P388 or P388/VCR. The LI is also increased in this direction. Therefore, it can be concluded that, depending on the kind of drug which made the MDR, different biochemical mechanisms are activated.