Effects of acivicin and dipyridamole on hepatoma 3924A cells

Abstract

Dipyridamole inhibited the incorporation of cytidine, thymidine, uridine, and guanosine in rat hepatoma 3924A cells with 50% inhibitory concentrations of 0.2 to 0.5 microM. For deoxycytidine, the 50% inhibitory concentration was about 100 times higher (23.8 microM). Addition of a combination of cytidine, deoxycytidine, and guanosine, at an optimal concentration of 80 microM each, protected the hepatoma cells from the growth-inhibitory action of the antiglutamine drug, acivicin. The protection provided by the nucleosides was blocked by dipyridamole (6 microM), but not by nitrobenzylthionosine (30 microM). The effect on cell survival of graded concentrations of 0.25 to 1.75 microM acivicin plus dipyridamole (5 microM) and 80 microM concentrations each of cytidine, deoxycytidine, and guanosine was investigated. At an acivicin concentration of 1.75 microM, survivals in the different groups were: (a) acivicin alone, 1%; (b) acivicin plus dipyridamole, 1%; (c) acivicin plus nucleosides, 78%; and (d) acivicin plus nucleosides plus dipyridamole, 3%. Acivicin and dipyridamole were cytotoxic for hepatoma 3924A cells with 50% inhibitory concentrations of 0.5 and 20.3 microM, respectively, as measured by clonogenic assay.