Distribution of cisplatin in bone marrow cells: quantitative X-ray imaging

The distribution of cisplatin in freeze-dried cryosections of rabbit bone marrow cells was measured with an imaging system. Cisplatin contains a single atom of platinum per molecule which allowed the concentration of the drug to be measured throughout the cryosections. This technique was chosen because it does not require the separation of cells into homogeneous subpopulations. X-ray imaging measured not only the distribution of the element labeling the drug, but also other elements which were used to follow the effect of the drug on membrane ion transport. 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 cells were found to accumulate this drug, while in the smaller more mature cells platinum could not be detected. Most of the platinum accumulated in the cytoplasm and was not evenly distributed. Cells containing high levels of platinum lost their cytoplasmic potassium and gained extracellular sodium and chloride. In some cases cells that contain lower concentrations of platinum with normal levels of potassium were found, indicating that the alteration of the membrane permeability or the inhibition of the K/Na pump did not occur during the initial accumulation of the drug. This membrane permeability or pump change requires the accumulation of high concentrations of the drug, resulting in the loss of potassium and the gain of sodium.