DISTRIBUTION OF CISPLATIN IN BONE-MARROW CELLS - QUANTITATIVE X-RAY-IMAGING

The distribution of cisplatin in freeze-dried cryosections of rabbit b one marrow cells was measured with an imaging system. Cisplatin contai ns a single atom of platinum per molecule which allowed the concentrat ion of the drug to be measured throughout the cryosections. This techn ique was chosen because it does not require the separation of cells in to homogeneous subpopulations. X-ray imaging measured not only the dis tribution of the element labeling the drug, but also other elements wh ich were used to follow the effect of the drug on membrane ion transpo rt. In samples incubated for 10 hr in cisplatin a high selectivity in the uptake of this drug was observed. Only a few of the large early ce lls were found to accumulate this drug, while in the smaller more matu re cells platinum could not be detected. Most of the platinum accumula ted in the cytoplasm and was nor evenly distributed. Cells containing high levels of platinum lost their cytoplasmic potassium and gained ex tracellular sodium and chloride. In some cases cells that contain lowe r concentrations of platinum with normal levels of potassium were foun d, indicating that the alteration of the membrane permeability or the inhibition of the K/Na pump did not occur during the initial accumulat ion of the drug. This membrane permeability or pump change requires th e accumulation of high concentrations of the drug, resulting in the lo ss of potassium and the gain of sodium. (C) 1995 Academic Press, Inc.