| Abstrakt: |
The biological consequence of the binding of cis-dichlorodiammineplatinum(II) (cis-DDP) to serum protein as well as to cellular components in general, was studied on human NHIK 3025 cells in vitro. As expected, we found that the cytotoxicity of cis-DDP was lost by binding to serum protein, and that protein-bound platinum was impermeable to the cells. As we have previously shown that electropermeabilisation may transiently increase the influx of cis-DDP, we applied this technique in an attempt to increase the efflux of cis-DDP or any other cytotoxic intermediates. Our data demonstrate that if cells are electropermeabilised shortly after treatment with cis-DDP, cell survival increased. This indicates that cis-DDP in an active form is released from the cells; furthermore, the plasma membrane represents a barrier against efflux, as it has also been shown to be against influx of active cis-DDP. Thus, our data are consistent with the idea that there must be an intracellular pool of either cis-DDP, or some biologically active intermediates, in cells treated with this drug. Additionally, our data indicate that the binding rate of cis-DDP to biological molecules is much quicker intracellularly than in the extracellular environment: We found the biological half-life at 37 degrees C to be about 2.1 h in human serum and about 11 min inside our cells. |
