Relationship between enhancement of cytotoxic effect of mitomycin C and increase of intracellular cyclic adenosine 3':5'-monophosphate by isoproterenol in rat ascites hepatoma cells.

Abstract

Cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels in six lines of rat ascites hepatoma cells were determined after the treatment with isoproterenol. The maximum increase of cyclic AMP levels was induced by the treatment with 10(-7) M of isoproterenol in each cell line, though the difference was observed at the time to reach the maximum levels. Following the treatment with 10(-7) M of isoproterenol, cyclic AMP levels increased by 55 to 80% of control in AH-44, AH-130 and AH-7974 cells, by 25 to 45% in AH-41C and AH-109A cells, and slightly in AH-13 cells. The combined cytotoxic effect of isoproterenol and mitomycin C was studied using AH-13, AH-44 and AH-130 cells. The cytotoxicity of mitomycin C on AH-44 and AH-130 cells was potentiated by the pretreatment with 10(-7) M of isoproterenol that was not cytotoxic by itself, but such a potentiation was not observed in AH-13 cells. The cyclic AMP levels were examined in the cells after the combined treatment. Mitomycin C by itself hardly affected the levels in three cell lines. In AH-44 and AH-130 cells, however, the period of the high levels of cyclic AMP was longer in the combined treatment than in the treatment with isoproterenol alone. On the other hand, the cyclic AMP level in AH-13 cells was hardly affected by each agent or the combined treatment. These results suggest that the combination effect of isoproterenol and mitomycin C is closely related to the increase of cyclic AMP in the cells treated with isoproterenol.