Patterns of anthracycline retention modulation in human tumor cells

Abstract

Laser excitation of cellular doxorubicin and daunomycin content (with or without incubation in the presence of efflux blockers such as phenothiazines or verapamil) was studied in cells from leukemic peripheral blood, bone marrow aspirates, and ascites and pleural fluid of solid tumor patients. Selected examples are presented to show that heterogeneity in cellular anthracycline retention as well as sensitivity to efflux modulators is seen in human tumor cells. Several tumor subpopulations differing in their cellular retention of anthracyclines or sensitivity to modulators were seen. In serial tumor samples from patients (pre- and post-treatment with anthracycline-containing protocols), initial drug retention and sensitivity to efflux modulators was followed by lack of drug retention and insensitivity to modulators. The present study shows that in view of the variables encountered in drug-retention characteristics and sensitivity to efflux modulators, one needs to screen tumor samples before recommending use of any particular transport modulator to enhance drug retention and sensitivity of drug-resistant cells.