Cell-killing efficiency and number of platinum atoms binding to DNA, RNA and protein molecules of HeLa cells treated with combinations of trans-diaminedichloroplatinum(II) and hyperthermia

The effect of hyperthermia on the cell-killing efficiency of Pt atoms binding to DNA, RNA and protein molecules was examined. HeLa S-3 cells were treated with 195mPt-radiolabeled trans-diaminedichloroplatinum(II) (TDDP) for 60 min at various temperatures, and the relationship between the lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentration (D0) of TDDP for a 60-min treatment at 0, 25, 37, 40, 42 and 44degC was 1714, 1016, 302, 179, 125 and 42.5μM, respectively. (D0 is defined as the dose that would give an average of one lethal event per member of the population. By using identically treated cells, the numbers of Pt-atoms combined with DNA, RNA and protein molecules were determined in the subcellular fractions. Thus, the D0's given as the drug concentrations were replaced with the number of Pt-atoms combined in each fraction. Then, the cell-killing efficiency of the Pt atom was expressed as the reciprocal of the number of Pt-atoms combined and was calculated for each molecule. The efficiency for DNA was 0.206, 0.273, 0.779, 1.28, 1.77 and 5.14 x 103 nucleotides, respectively, for the conditions described above. It seemed that hyperthermia potentially interacted not only with bifunctional, but also with monofunctional bonds. Thus, it was concluded that TDDP was markedly less cytotoxic than cis-diaminedichloroplatinum (CDDP) at 37degC, but was more cytotoxic than CDDP at 44degC. (author)