DETERMINATION OF THE TARGET VOLUME OF HELA-CELLS TREATED WITH PT-195M RADIOLABELED CIS-DIAMINE(1,1-CYCLOBUTANE-DICARBOXYLATO)PLATINUM(II) - COMPARISON WITH CIS-DIAMINEDICHLOROPLATINUM(II) AND TRANS-DIAMINEDICHLOROPLATINUM(II)

HeLa S-3 cells were treated with (195m)pt-radiolabeled cis-diammine(1,1-cyclobutane-dicarboxylato)platinum(II) (carboplatin) 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 carboplatin at 37 degrees C for 1, 2 and 3 h were 553.4, 194.3 and 68.7 mu M, respectively. By using identically treated cells, the numbers of Pt-atoms combined with DNA, RNA and protein molecules were determined after fractionation of the cells. In this way the D-0 values (D-0, dose that would give an average of one lethal event per member of the population), expressed as the drug concentration, were substituted for the number of Pt atoms combined with each fraction. The target volumes, the efficiency of Pt atom to kill cells expressed as the reciprocals of the D-0 values, were then calculated with each fraction. The results suggested that DNA was the primary target for cell killing by carboplatin. The target volumes for DNA were 0.891 x 10(4), 2.01 x 10(4) and 3.96 x 10(4) nucleotides for 1, 2 and 3 h treated cells, respectively. The cell killing effects of carboplatin were lower than those of cis-diaminedichloroplatinum(II) (CDDP) by factors of 6.0, 2.8 and 2.6 for 1, 2 and 3 h treatments at 37 degrees C, respectively, in terms of the target volume, while those in terms of the mean lethal dose (D-0) were 59.5, 29.0 and 21.5, respectively.