Reduction of cis-dichlorodiammineplatinum-induced cell inactivation by benzaldehyde

Abstract

The inactivating effect of a combined treatment of human cells (NHIK 3025) in culture with cis-dichlorodiammineplatinum(II) (cis-DDP) and the protein synthesis inhibitor benzaldehyde was tested. Cell inactivation was measured as loss of colony-forming ability following drug treatment. While 3.2 mM benzaldehyde had no effect on the cell survival when given alone, it reduced the effect of 10 microM cis-DDP significantly when the two drugs were added simultaneously. Scheduling experiments indicate that benzaldehyde must be present immediately before addition of, or simultaneously with, cis-DDP for optimal reduction of cell inactivation. Benzoic acid, benzyl alcohol or the protein synthesis inhibitor cycloheximide did not reduce the inactivating effect of cis-DDP. Cells synchronized by mitotic selection were used to determine the variation in the responses throughout the cell cycle. It was found that concomitant 2-hr treatment of synchronized cells with 3.2 mM benzaldehyde and 10 microM cis-DDP at various times during the cell cycle resulted in a consistently greater surviving fraction of cells than 10 microM cis-DDP alone. Benzaldehyde thus reduced the inactivating effect of cis-DDP in all phases of the cell cycle. The effect of benzaldehyde in combination with two alkylating agents, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and nitrogen mustard (HN2), was also studied. Benzaldehyde was not found to influence the effects on cell survival induced by these drugs.