Send to

Choose Destination
Anticancer Drugs. 1993 Apr;4(2):251-8.

Differential cytotoxicity, uptake and DNA binding of tetraplatin and analogous isomers in sensitive and resistant cancer cell lines.

Author information

Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston 77030.


Some platinum complexes contain 1,2-diaminocyclohexane (DACH) as a stable carrier ligand, which can exist as the R,R-, S,S- and cis-isomers. Tetraplatin, for instance, is a mixture of R,R- and S,S-DACH-Cl4-Pt(IV). We have examined each of the three individual isomers of DACH-Cl4-Pt(IV) with respect to cytotoxicity, uptake of platinum and total DNA-platinum in three murine leukemia L1210 (cisplatin-sensitive L1210/0, 50-fold cisplatin-resistant L1210/DDP and 36-fold tetraplatin-resistant L1210/DACH) and human ovarian carcinoma A2780 (cisplatin-sensitive) and A2780cp (8-fold cisplatin-resistant) cell lines. Against A2780, A2780cp and L1210/DDP cell lines, the R,R-isomer was the most potent followed by the S,S-isomer and then the cis-isomer. However, the three isomers demonstrated similar IC50 values against the L1210/0 and L1210/DACH cell lines. The cis-isomer demonstrated cross-resistance (9- to 20-fold) to cisplatin in L1210/DDP and A2780cp cell lines. On the other hand, R,R- and S,S-isomers demonstrated minimal (2- to 4-fold) cross-resistance against these tumor models. Intracellular platinum accumulation over a 2 h period at 40 microM drug concentration was significantly (p < 0.05) greater for the R,R-isomer than the cis-isomer in L1210/0 (122 versus 101 ng Pt/mg protein) and L1210/DDP (73 versus 50) cell lines, while no difference was observed in L1210/DACH cells (55 versus 56). In L1210/DDP cells, total DNA-bound platinum was significantly (p < 0.05) greater for the R,R-isomer compared with the cis-isomer (10.3 versus 7.5 ng Pt/mg DNA).(ABSTRACT TRUNCATED AT 250 WORDS).

[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center