Doxorubicin (Adriamycin) transport in Ehrlich ascites tumour cells: Comparison with transport in human red blood cells

Abstract

The doxorubicin (Adriamycin) transport was investigated in murine Ehrlich ascites tumour cells by measuring the initial rate of cellular net uptake in vitro at 37°C (pH 7.3). Transport characteristics were compared with previously published data on doxorubicin transport in human red blood cells. The apparent permeability coefficient in ascites cells (2.4 × 10⁻⁵ cm sec⁻¹) and in red cells was of the same order of magnitude when calculated from the initial influx into cells suspended in a salt solution (37°C, pH 7.3). Doxorubicin was strongly adsorbed to the cell surface of ascites cells in contrast to the doxorubicin adsorption to red cells when the cells were suspended in a salt solution. The adsorbed doxorubicin could be removed by washing the ascites cells either with DNA or with human albumin salt solutions indicating that the adsorption to cell surface components was reversible. Cell membrane modifiers, 1-alcohols, local anaesthetics, phloretin, HgCl₂, para-chloromercuribenzoate, affected doxorubicin transport in ascites tumour cells and red cells in the same manner as these modifiers affected the transport of other lipophilic compounds. Ehrlich ascites tumour cells and human red blood cells appeared to represent two extremes with regard to doxorubicin adsorption to cell surfaces but doxorubicin seems to pass through the rate limiting barrier of the cell membrane by simple diffusion of the uncharged doxorubicin molecule in both cell types.

Key Words:

• 1-alcohols
• cancer cells
• diffusion
• HgCl₂
• lipophilic compounds
• local anaesthetic
• parachloromercuribenzoate
• phloretin