Increase in Nonspecific Adsorptive Endocytosis in Anthracycline-and Vinca Alkaloid-Resistant Ehrlich Ascites Tumor Cell Lines2

Abstract

Numerous biochemical and drug transport studies have focused on the role of the plasma membrane or membrane-associated processes in anthracycline and vinca alkaloid resistance. Cationized ferritin, which binds electrostatically to anionic sites on the plasma membrane, was used as a membrane marker in a morphometrical ultrastructural study. The nonspecific adsorptive endocytosis was significantly increased in Ehrlich ascites tumor cell lines resistant to daunorubicin (DNR), doxorubicin, vincristine, and vinblastine compared to that in sensitive cells. Thus cells resistant to DNR internalized 2.04% of their plasma membrane per minute, in contrast to 1.17% in sensitive cells. Because the measured cell surface areas in sensitive and resistant cells were unchanged during the experiments, increased membrane traffic (recycling) from intracytoplasmic compartments to the plasma membrane must have occurred in resistant cells. Possible implications of these findings include 1) a resistance-linked phenotype without significance for resistance per se, 2) an increase in membrane repair, and 3) a connection between increased membrane traffic and increased active drug extrusion in resistant cells.