Sex-dependent differences in the biosynthesis of pyrimidine nucleotides in rat liver after repeated administration of alpha-hexachlorocyclohexane.

Utilization of [2-14C]orotic acid for the synthesis of the pyrimidine components of the free nucleotide pool and RNA from isolated cytoplasmic ribosomes was investigated in the liver of female and male rats. In females, labeled orotic acid is incorporated relatively more into uridine than into cytidine nucleotides; the opposite is true for males. The administration of alpha-hexachlorocyclohexane (alpha-HCH) decreases the specific radioactivity of rRNA cytidylic acid more in males than in females. Simultaneously, the level of liver microsomal cytochrome P-450 is increased after the administration of alpha-HCH more in males than in females. After four days of treatment with alpha-HCH, the concentrations of the uridine and cytidine components of the acid-soluble pool are slightly depressed. Following repeated administration of alpha-HCH, the utilization of labeled uridine for the synthesis of cytidine nucleotides of the acid-soluble pool and RNA is depressed, whereas that of labeled cytidine is enhanced. Repeated administration of alpha-HCH decreases the utilization of [2-14C]orotic acid for the synthesis of cytidine nucleotides of DNA; the specific radioactivity of thymidylic acid is increased. The administration of beta-diethylaminoethyl diallylacetate (CFT-1201) to animals that have repeatedly received alpha-HCH decreases the specific radioactivity of DNA thymine.