Quantitative analysis of anthracyclines kinetics in cells varying in drug responsiveness

摘要

Abstract: A fluorimetric technique to measure transport parameters of fluorescent drugs through cellular membranes is described. This method eliminates procedures that would lead to errors in the measurement of drug accumulated by cells, and measures the fraction of free drug in cells. The use of a simple three-compartment model in conjunction with fluorescence measurements performed on the extracellular medium and on Triton-permeabilized cells at different times during daunorubicin incorporation allows determination of the kinetic parameters of the transport through cellular membranes. With this technique we found that LoVo cells have a greater daunorubicin uptake, a similar input rate constant and a lower output rate constant than the drug resistant LoVo/DX cells. Preliminary photoactivation measurements of these two cell lines with these compounds showed that phototoxic effects are related to the amount of drug bound to cellular sites. !33