Multidrug resistance modifies polyamines uptake in P388 murine lymphoma cells: experimental and modeling approach

Polyamines (putrescine, spermidine and spermine) are ubiquitous compounds, essential for cell growth. This paper compares the polyamine transport betw een sensitive P388 murine lymphoma cells and two multidrug resistant P388 s ublines with the assistance of an experimental model. This new model allows the characterisation of the whole polyamines uptake and efflux. Three para meters are identified by the model: two rate constants (K+ for the uptake a nd K- for the efflux) which are considered as physical constants specific t o the transport of one polyamine in one cell type, and Ci(o) which represen ts the initial intracellular concentration. This model well describes our e xperimental results of polyamine transport across the P388 cell plasma memb rane. Multidrug resistant P388 cells exhibit spermine uptake significantly higher than that of sensitive cells when on the opposite, putrescine enters more rapidly into the sensitive P388 cells. In conclusion, comparison of p olyamine transport between sensitive and multidrug resistant P388 phenotype s shows large and significant differences. (C) 1999 Elsevier Science B.V. A ll rights reserved.