In vitro uptake of gallium and chlorpromazine by mouse tumour cells

Primary cell suspensions were prepared from mouse sarcoma by enzymatic digestion with pronase. The cells were incubated with gallium citrate Ga 67 or the basic drug 14C-chlorpromazine (CPZ) for up to 1 h at 37 degrees C, and the label uptake was determined. The Ga uptake was proportional to time (0-30 min), whilst the CPZ uptake rapidly reached apparent saturation (less than 10 min). Metabolic inhibitors did not affect label uptake; however, disrupting the cell membrane with N-ethylmaleimide or heating at 56 degrees C significantly reduced CPZ accumulation but did not inhibit Ga uptake. Ga accumulation was decreased by adding human transferrin (0.5 mg/ml). Both gallium and chlorpromazine are fixed in the lysosomes of cells; however, in this system, they appeared to enter mouse sarcoma cells by different energy-independent mechanisms. The Ga uptake may reflect adsorption to cell components, whilst CPZ uptake required an intact cell and may be due to passive diffusion.