Reduced cellular uptake of cis-dichlorodiammine-platinum by benzaldehyde

Synchronized human NHIK 3025 cells were treated with cis-dichlorodiammineplatinum (cis-DDP) either alone or in combination with benzaldehyde as a 2 h pulse in G1-phase. After this pulse, the cells entered S-phase and the rate of DNA synthesis was measured by DNA-flow cytometric recordings of serial samples. After treatment with 10 microM cis-DDP alone, the rate of DNA synthesis was 38% of the control rate. If 3.2 mM benzaldehyde was present together with 10 microM cis-DDP, the rate of DNA synthesis was 56% of the control rate, this being similar to the rate measured following treatment of cells with 5 microM cis-DDP alone. Thus, the simultaneous presence of benzaldehyde with cis-DDP mitigates the inhibition of DNA synthesis induced by cis-DDP. However, when cells were electropermeabilized during the treatment pulse, benzaldehyde did not protect the cells from cis-DDP-induced cell inactivation. The protective effect of benzaldehyde thus seems to reside with the cell membrane and it seems that benzaldehyde, when present together with cis-DDP, partially inhibits the uptake of cis-DDP into cells. Atomic absorption spectroscopy confirmed that the simultaneous presence of 5 mM benzaldehyde halved the amount of cell-bound platinum from that measured following treatment with cis-DDP alone.