Effect of copper and cadmium pretreatments on DNA synthesis and thymidine kinase activity in the liver of dimethylnitrosamine-treated and partially hepatectomized rats.

Dose-related suppression of the 3H-thymidine incorporation into liver DNA of rats after a single injection of dimethylnitrosamine by copper pretreatment was observed. The 3H-thymidine incorporation was not decreased by cadmium pretreatment. On the other hand, the 3H-thymidine incorporation into liver DNA of partially hepatectomized rats was decreased by both copper and cadmium pretreatments. Thymidine kinase activity in the liver of rats treated with dimethylnitrosamine was also decreased by copper pretreatment, but the enzyme activity was not decreased by cadmium pretreatment. Copper accumulation in the liver of copper-administered rats was predominantly in the nuclear fraction, followed by the soluble fraction. Cadmium accumulation in the liver of cadmium-administered rats was predominantly in the soluble fraction, followed by the nuclear fraction. Copper accumulation in the nuclear fraction may suppress the induction of thymidine kinase in the liver of rats by dimethylnitrosamine.