The Number of Platinum Atoms Binding to DNA, RNA and Protein Molecules of HeLa Cells Treated with Cisplatin at Its Mean Lethal Concentration

Abstract

HeLa S‐3 cells were treated with 195mPt‐radiolabeled cis‐diamminedichloroplatinum(II) (CDDP) under various conditions, and the relationship between lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentrations for the cells treated with CDDP at 37°C for 1, 2 and 3 h were 2.8, 2.0 and 1.1 μg/ml, respectively. By using identically treated cells, the number of Pt atoms combined with DNA, RNA and protein molecules were determined after fractionation of the cells using the method of Schneider. In this way, the Do values given as the drug concentration were substituted for the number of Pt atoms combined with each fraction, then the target volumes expressed as the reciprocals of Do values were calculated for each fraction. The results provide strong support for the idea that DNA is the primary target for cell killing by CDDP, and the target volumes were 5.17 × 104, 5.71 × 104 and 1.03 × 104 nucleotides for 1, 2 and 3 h treated cells, respectively.