DETERMINATION OF THE TARGET VOLUME OF HELA-CELLS TREATED WITH TETRA-CHLOROPLATINATES AND HEXA-CHLOROPLATINATES

HeLa S-3 cells were treated with Pt-195m-radiolabeled tetra- and hexa-chloroplatinums (Pt(II) and Pt(IV)) 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 Pt(II) at 37-degrees-C for 1, 2 and 3 h were 163.5, 126.2 and 67.3 muM, while those for Pt(IV) were 78.6, 53.4 and 35.9, respectively. By using identically treated cells, the number of Pt-atoms combined with DNA, RNA and protein molecules were determined after the cell were fractionated using the method of Schneider [ref. 1]. In this way, the D(o) values given as the drug concentration were substituted for the number of Pt-atoms combined with each fraction, then, die target volumes expressed as the reciprocals of D(o) values were calculated for each fraction. The results suggested that DNA and high molecular weight RNAs (except t-RNA), under some limited condition, can be the target molecules for cell killing by both the compounds. The target volumes for DNA were 3.15x10(3), 3.75x10(3) and 5.86x10(3) nucleotides for 1.2 and 3 h Pt(II)-treated cells, while those for Pt(IV) were 4.27x10(3), 4.58x10(3) and 6.37x10(3) nucleotides, respectively. This means that no significant difference between the two platinates can be detected on the efficiency for Pt-atom to kill the cell. Cell killing effects of Pt(IV) was lower than CDDP (see ref. 7) by a factor of 12-16 according to the treatment, but higher than TDDP (see ref. 8) by a factor of 1.4-2.5.