Effect of nafenopin and clofibrate on uptake and utilization of labeled thymidine for DNA synthesis in rat liver and kidney.

The mitogenic effect of nafenopin and clofibrate in the liver is paralleled by a decreased utilization of [14C]thymidine for kidney DNA synthesis. Analogous changes in the liver and kidney DNA biosynthesis after nafenopin administration occur if [14C]orotic acid is added as a precursor of DNA pyrimidines. There is a time correlation between the uptake of labeled thymidine and its utilization for DNA synthesis in the liver during the initial stages of the mitogenic effect of the drug. Later on--after administration of a low dose of nafenopin or of repeated doses of clofibrate--the specific activity of DNA thymine does not differ from the values observed with the control group: the total radioactivity of the thymine components of the acid-soluble extract is even increased. The existence of a correlation between decreased utilization of [14C]thymidine for DNA synthesis and the total radioactivity of the thymine components of the acid-soluble extract in kidney can be observed only during the early stages after nafenopin administration. Subsequently, when the depression of the specific activity of kidney DNA thymine still persists, the specific activity of the thymine components of the acid-soluble extract does not differ from control values. The utilization of [14C]thymidine for DNA synthesis in the kidney is decreased after repeated clofibrate administration only 24 h after the last dose of the drug; these values later increase and even exceed control values. The total radioactivity of the thymine components of the kidney acid-soluble extract is unchanged.