Liver growth, biosynthesis of cytidine nucleotides and level of cytochrome P-450 in rat liver after administration of α-hexachlorocyclohexane

Abstract

The biosynthesis of cytidine nucleotides and the level of microsomal cytochrome P-450 in intact and regenerating rat liver after repeated administration of α-hexachlorocyclohexane (α-HCH) were compared. In α-HCH treated animals the utilization of [2- 14C]orotic acid for the synthesis of cytidine nucleotides is suppressed. In 24-h regenerating liver the incorporation of labelled orotic acid into cytidine nucleotides is markedly activated; the degree of activation is lower in regenerating livers of α-HCH treated animals. The changes in the level of cytochrome P-450 vary inversely with the changes in the utilization of [2- 14C]orotic acid for the synthesis of cytidine nucleotides. The activity of cytidine triphosphate synthetase of liver cytosol increases shortly after the administration of α-HCH; uridine-cytidine kinase is enhanced in the later stages of the drug action. Within 15–45 min after the administration of α-HCH the uptake of [U- 14C]cytidine into the liver and its incorporation into RNA cytosine are increased. After the administration of the drug the uptake of [2- 14C]uridine and its incorporation into RNA uracil is also enhanced whereas its utilization for the synthesis of cytidine nucleotides of the acid-soluble extract as well as for the RNA cytosine are suppressed.