| Research Abstract |
Six kinds of ^<195m>Pt radiolabeled Pt compounds, cis- and trans-diaminedichloroplatinums(II) (CDDP and TDDP), cis-diamine(1, 1-cycrobutanedicarboxylato) platinum(II) (CBDCA), (-)-(R)-2-aminomethylpyrrolidine(1, 1-cyclobutanedicarboxylato)-2-platinum(II) (DWA2114R), and tetra- and hexa-chloroplatinates (Tetra-Pt and Hexa-Pt) were synthesized in our laboratory.
HeLa cells were treated with the six kinds of ^<195m>Pt-radiolabeled Pt-compounds under various conditions, and the relationships between lethal effect and the number of Pt atoms binding to DNA, RNA and protein molecules were examined. At first, we determined the mean lethal concentration (D_0) from the semilogarithmic dose-survival curves of the cells treated with these compounds. Then the D_0 values given as the drug concentration were substituted for the number of Pt atoms combined with biologically important molecules. Finally we calculated the target volumes (efficiency of Pt atom to kill the cells) expressed as the reciprocals of D_0s.
The mean lethal concentrations (D_0) for the cells treated with CDDP, Hexa-Pt, DWA2114R, Tetra-Pt, TDDP and CBDCA at 37ﾟC for 1 h were 9.3, 78.6, 137.3, 163.5, 163.7 and 553.4 muM, respectively. Namely, lethal effects of the Pt-compounds decreased in that order when viewed from the stand point of the D_0. However, the order somewhat varied when we compared the effect from the stand point of the target volume. The target volumes of DNA were 5.17, 3.36, 0.891, 0.043, 0.032 and 0.013X10^4 nucleotides for CDDP, DWA2114R, CBDCA, Hexa-Pt, Tetra-Pt and TDDP, respectively. The difference in the order of lethal action of these Pt-compounds between the D_0 and the target volume can be ascribcd in part to the different ability of these compounds to bind to DNA molecules, and another part to the different efficiency of Pt atom to kill the cells.
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