DETERMINATION OF THE TARGET VOLUME OF HELA-CELLS TREATED WITH PT-195MRADIOLABELED 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 iammine(1,1-cyc lobutane-dicarboxylato)platinum(II) (carboplatin) under various condit ions, and the relationship between lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal c oncentrations for the cells treated with carboplatin at 37 degrees C f or 1, 2 and 3 h were 553.4, 194.3 and 68.7 mu M, respectively. By usin g 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 avera ge of one lethal event per member of the population), expressed as the drug concentration, were substituted for the number of Pt atoms combi ned with each fraction. The target volumes, the efficiency of Pt atom to kill cells expressed as the reciprocals of the D-0 values, were the n calculated with each fraction. The results suggested that DNA was th e primary target for cell killing by carboplatin. The target volumes f or DNA were 0.891 x 10(4), 2.01 x 10(4) and 3.96 x 10(4) nucleotides f or 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 thos e in terms of the mean lethal dose (D-0) were 59.5, 29.0 and 21.5, res pectively.