Protection from cis-dichlorodiammineplatinum-induced cell inactivation by aldehydes involves cell membrane amino groups

Abstract

The effect of cis-dichlorodiammineplatinum (cis-DDP) alone or in combination with the vitamin B6 analogs pyridoxal, pyridoxal 5'-phosphate and pyridoxine was tested on human NHIK 3025 cells. Cell inactivation was measured as loss of colony-forming ability following 2 h drug treatment. The cell inactivating effect of cis-DDP was significantly reduced when the aldehyde analogs pyridoxal or pyridoxal 5'-phosphate were simultaneously present with cis-DDP. The alcohol analog pyridoxine, however, did not affect cis-DDP-induced cell inactivation to any degree. Pyridoxine, pyridoxal or pyridoxal 5'-phosphate treatment alone had no effect on cell survival. Both pyridoxal and pyridoxal 5'-phosphate form Schiff bases with protein amino groups, but pyridoxal 5'-phosphate is cell membrane-impermeable. Therefore protection from cis-DDP-induced cell inactivation by aldehydes appears to involve cell membrane amino groups.