INHIBITION OF DNA SYNTHESIS IN LIVER AND HEPATOMA CELLS BY CYCLOHEPTIMIDAZOLON DERIVATIVES

Abstract

Cycloheptimidazolon is a compound similar to benzimidazolon but with seven-members ring instead of benzene ring. One of these compounds, 1 (2-dimethylaminothyl) cycloheptimidazole-2 (1 H) -one was injected intraperitoneally with ³²P to the rats bearing regenerating liver. In those rats, DNA synthesis was observed 2 hours earlier than the control rats. Thymidine kinase extracted from the same regenerating liver was found markedly enhanced. On the contrary, when rat ascitic hepatoma (AH 130) was incubated in vitro for 60 minutes with ³H-thymidine and 8 mM of cycloheptimidazolon derivatives, remarkable inhibition was observed. In these cases, although an appreciable inhibition was not found in thymidine kinase activity by these compounds, DNA polymerase extracted from hepatoma cells was suppressed by in vitro addition of cycloheptimidazolon derivatives. Thus, these compounds showed a selective inhibition on DNA synthesis in cancer cells but not on DNA replication in regenerating liver.